Association between higher duodenal levels of the fructose carrier glucose transporter-5 and nonalcoholic fatty liver disease and liver fibrosis.

BACKGROUND: An increased dietary fructose intake has been shown to exert several detrimental metabolic effects and contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). An augmented intestinal abundance of the fructose carriers glucose transporter-5 (GLUT-5) and glucose transporter-2 (GLUT-2) has been found in subjects with obesity and type 2 diabetes. Herein, we investigated whether elevated intestinal levels of GLUT-5 and GLUT-2, resulting in a higher dietary fructose uptake, are associated with NAFLD and its severity. METHODS: GLUT-5 and GLUT-2 protein levels were assessed on duodenal mucosa biopsies of 31 subjects divided into 2 groups based on ultrasound-defined NAFLD presence who underwent an upper gastrointestinal endoscopy. RESULTS: Individuals with NAFLD exhibited increased duodenal GLUT-5 protein levels in comparison to those without NAFLD, independently of demographic and anthropometric confounders. Conversely, no difference in duodenal GLUT-2 abundance was observed amongst the two groups. Univariate correlation analyses showed that GLUT-5 protein levels were positively related with body mass index, waist circumference, fasting and 2 h post-load insulin concentrations, and insulin resistance (IR) degree estimated by homeostatic model assessment of IR (r = 0.44; p = 0.02) and liver IR (r = 0.46; p = 0.03) indexes. Furthermore, a positive relationship was observed between duodenal GLUT-5 abundance and serum uric acid concentrations (r = 0.40; p = 0.05), a product of fructose metabolism implicated in NAFLD progression. Importantly, duodenal levels of GLUT-5 were positively associated with liver fibrosis risk estimated by NAFLD fibrosis score. CONCLUSION: Increased duodenal GLUT-5 levels are associated with NAFLD and liver fibrosis. Inhibition of intestinal GLUT-5-mediated fructose uptake may represent a strategy for prevention and treatment of NAFLD.

The Many Faces of Metabolic Dysfunction-Associated Fatty Liver Disease Treatment: From the Mediterranean Diet to Fecal Microbiota Transplantation.

The gastrointestinal tract is inhabited by the gut microbiota. The main phyla are Firmicutes and Bacteroidetes. In non-alcoholic fatty liver disease, now renamed metabolic dysfunction-associated fatty liver disease (MAFLD), an alteration in Firmicutes and Bacteroidetes abundance promotes its pathogenesis and evolution into non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. For this reason, early treatment is necessary to counteract its progression. The aim of the present narrative review is to evaluate the different therapeutic approaches to MAFLD. The most important treatment for MAFLD is lifestyle changes. In this regard, the Mediterranean diet could be considered the gold standard in the prevention and treatment of MAFLD. In contrast, a Western diet should be discouraged. Probiotics and fecal microbiota transplantation seem to be valid, safe, and effective alternatives for MAFLD treatment. However, more studies with a longer follow-up and with a larger cohort of patients are needed to underline the more effective approaches to contrasting MAFLD.

Atrial fibrillation and QT corrected. What is the best formula to use?

BACKGROUND: QT interval varies with the heart rate (HR), so a correction in QT calculation is needed (QTc). Atrial fibrillation (AF) is associated with elevated HR and beat-to-beat variation. AIM: To find best correlation between QTc in atrial fibrillation (AF) versus restored sinus rhytm (SR) after electrical cardioversion (ECV) (primary end point) and to determine which correction formula and method are the best to determine QTc in AF (secondary end point). METHODS: During a 3-month period, we considered patients who underwent 12-lead ECG recording and received an AF diagnosis with indication for ECV. Exclusion criteria were as follows: QRS duration >120 ms, therapy with QT-prolonging drugs, a rate control strategy and a nonelectrical cardioversion. The QT interval was corrected using Bazzett's, Framingham, Fridericia and Hodges formulas during the last ECG during AF and the first one immediately after ECV. QTc mean was calculated as mQTc (average of 10 QTc calculated beat per beat) and as QTcM (QTc calculated from the average of 10 raw QT and RR for each beat). RESULTS: Fifty consecutive patients were enrolled in the study. Bazett's formula showed a significant change in mean QTc value between the two rhythms (421.5 ± 33.9 vs. 446.1 ± 31.9; p < 0.001 for mQTc and 420.9 ± 34.1 vs. 441.8 ± 30.9; p = 0.003 for QTcM). On the contrary, in patients with SR, QTc assessed by the Framingham, Fridericia, and Hodges formulas was similar to that in AF. Furthermore, good correlations between mQTc and QTcM are present for each formula, even in AF or SR. CONCLUSIONS: During AF, Bazzett's formula, seems to be the most imprecise in QTc estimation.

The r'-Wave Algorithm: A New Diagnostic Tool to Predict the Diagnosis of Brugada Syndrome after a Sodium Channel Blocker Provocation Test.

A diagnosis of Brugada syndrome (BrS) is based on the presence of a type 1 electrocardiogram (ECG) pattern, either spontaneously or after a Sodium Channel Blocker Provocation Test (SCBPT). Several ECG criteria have been evaluated as predictors of a positive SCBPT, such as the ß-angle, the α-angle, the duration of the base of the triangle at 5 mm from the r'-wave (DBT- 5 mm), the duration of the base of the triangle at the isoelectric line (DBT- iso), and the triangle base/height ratio. The aim of our study was to test all previously proposed ECG criteria in a large cohort study and to evaluate an r'-wave algorithm for predicting a BrS diagnosis after an SCBPT. We enrolled all patients who consecutively underwent SCBPT using flecainide from January 2010 to December 2015 in the test cohort and from January 2016 to December 2021 in the validation cohort. We included the ECG criteria with the best diagnostic accuracy in relation to the test cohort in the development of the r'-wave algorithm (ß-angle, α-angle, DBT- 5 mm, and DBT- iso.) Of the total of 395 patients enrolled, 72.4% were male and the average age was 44.7 ± 13.5 years. Following the SCBPTs, 24.1% of patients (n = 95) were positive and 75.9% (n = 300) were negative. ROC analysis of the validation cohort showed that the AUC of the r'-wave algorithm (AUC: 0.92; CI 0.85-0.99) was significantly better than the AUC of the ß-angle (AUC: 0.82; 95% CI 0.71-0.92), the α-angle (AUC: 0.77; 95% CI 0.66-0.90), the DBT- 5 mm (AUC: 0.75; 95% CI 0.64-0.87), the DBT- iso (AUC: 0.79; 95% CI 0.67-0.91), and the triangle base/height (AUC: 0.61; 95% CI 0.48-0.75) (p < 0.001), making it the best predictor of a BrS diagnosis after an SCBPT. The r'-wave algorithm with a cut-off value of ≥2 showed a sensitivity of 90% and a specificity of 83%. In our study, the r'-wave algorithm was proved to have the best diagnostic accuracy, compared with single electrocardiographic criteria, in predicting the diagnosis of BrS after provocative testing with flecainide.

Ultrasound Prevalence and Clinical Features of Nonalcoholic Fatty Liver Disease in Patients with Inflammatory Bowel Diseases: A Real-Life Cross-Sectional Study.

Background and Objectives: Inflammatory bowel disease (IBD) is a condition characterized by chronic intestinal inflammation. We can identify two major forms: Crohn's disease (CD) and ulcerative colitis (UC). One of the extraintestinal manifestations of IBD is nonalcoholic fatty liver disease (NAFLD). IBD and NAFLD share common pathogenetic mechanisms. Ultrasound (US) examination is the most commonly used imaging method for the diagnosis of NAFLD. This cross-sectional observational retrospective study aimed to evaluate the US prevalence of NAFLD in IBD patients and their clinical features. Materials and Methods: A total of 143 patients with IBD underwent hepatic US and were divided into two different groups according to the presence or absence of NAFLD. Subsequently, new exclusion criteria for dysmetabolic comorbidities (defined as plus) were applied. Results: The US prevalence of NAFLD was 23% (21% in CD and 24% in UC, respectively). Most IBD-NAFLD patients were male and older and showed significantly higher values for body mass index, waist circumference, disease duration, and age at onset than those without NAFLD. IBD-NAFLD patients showed a significantly higher percentage of stenosing phenotype and left-side colitis. Regarding metabolic features, IBD-NAFLD patients showed a significantly higher percentage of hypertension and IBD plus dysmetabolic criteria. Also, higher values of alanine aminotransferase and triglycerides and lower levels of high-density lipoproteins are reported in these patients. Conclusions: We suggest performing liver US screening in subjects affected by IBD to detect NAFLD earlier. Also, patients with NAFLD present several metabolic comorbidities that would fall within the new definition of metabolic-associated fatty liver disease. Finally, we encourage larger longitudinal studies, including healthy controls, to provide further confirmation of our preliminary data.

Metabolic-Dysfunction-Associated Fatty Liver Disease and Gut Microbiota: From Fatty Liver to Dysmetabolic Syndrome.

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is the recent nomenclature designation that associates the condition of non-alcoholic fatty liver disease (NAFLD) with metabolic dysfunction. Its diagnosis has been debated in the recent period and is generally associated with a diagnosis of steatosis and at least one pathologic condition among overweight/obesity, type 2 diabetes mellitus, and metabolic dysregulation. Its pathogenesis is defined by a "multiple-hit" model and is associated with alteration or dysbiosis of the gut microbiota. The pathogenic role of dysbiosis of the gut microbiota has been investigated in many diseases, including obesity, type 2 diabetes mellitus, and NAFLD. However, only a few works correlate it with MAFLD, although common pathogenetic links to these diseases are suspected. This review underlines the most recurrent changes in the gut microbiota of patients with MAFLD, while also evidencing possible pathogenetic links.

Non-conducted premature atrial complexes: A new independent predictor of atrial fibrillation in cryptogenic stroke.

INTRODUCTION: Atrial fibrillation (AF) is the main cardiac cause of stroke, but it frequently remains undetected. In patients with cryptogenic stroke an Holter electrocardiogram (ECG) monitoring for AF is recommended. OBJECTIVE: To evaluate the prognostic role of Non-Conducted Premature Atrial Complexes (ncPACs) recorded on Holter ECG. METHODS: We prospectively enrolled consecutive patients admitted to the Stroke Unit of our hospital with a diagnosis of cryptogenic stroke between December 2018 and January 2020; all patients underwent 24-h Holter ECG monitoring during hospitalization. Two follow-up visits were scheduled, including a 24-h Holter ECG at 3 and 6 months to detect AF. RESULTS: Among 112 patients, 58% were male with an average age of 72.2 ± 12.2 years. At follow-up, AF was diagnosed in 21.4% of the population. The baseline 24-h Holter ECG burden of ncPACs and Premature Atrial Complexes (PACs) was higher in patients with AF detected on follow-up (13.5 vs 2, p = 0.001; 221.5 vs 52; p = 0.01). ROC analysis showed that ncPACs had the best diagnostic accuracy in predicting AF (AUC:0.80; 95% CI 0.68-0.92). Cut-off value of ≥7 for ncPACs burden showed the highest accuracy with sensitivity of 62.5% and specificity 97.7% to predict AF onset at follow-up. Moreover, at multivariate Cox-proportional hazard analysis ncPACs burden ≥7 was a powerful independent predictor of AF onset (HR 12.4; 95% CI 4.8-32.8; p < 0.0001). CONCLUSIONS: NcPACs burden ≥7 represents a new predictor of AF that could guide the screening of this arrhythmia in cryptogenic stroke patients.

The protective effects of resveratrol on ulcerative colitis via changing the profile of Nrf2 and IL-1ß protein.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with increasing incidence and prevalence in developed countries. The presence of inflammatory cytokines is considered the main detrimental factor in severe types of IBD. The Nrf2 transcription factor plays an important role in reducing the expression of inflammatory agents such as interleukin (IL)-1ß and increasing reparative factors such as IL-11. Resveratrol, a plant-derived phenolic compound, reduces the damage in chronic experimentally induced colitis. Twenty patients with UC and also 20 healthy controls were recruited in this study. The proteins expression of Nrf2 and IL-1ß was assessed in colonic biopsies by Western blotting. Caco-2 cells were challenged with TNF-α (in vitro simulation of UC), in the presence or not of 190 nM (24 h) and 75 nM (48 h) Resveratrol. Then, Nrf2 and IL-1ß in gene and protein expression were measured by real time-PCR and Western blotting in different treatments. Finally, IL-11 proteins expression was measured in culture supernatant by ELISA. A significant increase of IL-1ß protein was detected in inflamed colonic tissues from UC patients compared with the control individuals. In Caco-2 cells challenged with TNF-α, protein expression of IL-1ß and p-Nrf2 showed an increase, while gene expression of Nrf2 did not show a significant difference. After treatment with Resveratrol, both IL-1ß mRNA and protein levels were reduced, while IL-11 protein levels showed any increase. The p-Nrf2 is a dominant form which is prevalent in inflamed tissues from UC patients. Resveratrol can reverse the inflammatory effects of TNF-α by reducing IL-1ß and increasing IL-11 production.

COVID-19 and Inflammatory Bowel Disease: Patient Knowledge and Perceptions in a Single Center Survey.

Background and objectives: Spreading of SARS-CoV-2 infection from China to countries with a higher prevalence of inflammatory bowel disease (IBD) has generated concern among gastroenterologists and patients. The aim of this survey is to evaluate knowledge about clinical importance of COVID-19, disease management, prevention measures, and anxiety level during pandemic among patients with IBD. Material and methods: From 15th March to 15th April 2020, a questionnaire survey was administered to 200 patients with IBD by email or phone application. The questionnaire consisted of five sections: (1) anthropometric, demographic and clinical characteristics, (2) knowledge about clinical importance of COVID-19, (3) IBD management, (4) prevention measures, (5) anxiety level during pandemic. Results: One hundred forty two questionnaires were completed. Ninety-seven patients (68.3%) were males with a mean age of 46 years (SD 13; range 17-76). Fifty-four individuals (38%) were affected by Crohn disease and 88 (62%) by Ulcerative Colitis. Most patients reported high knowledge about clinical importance of COVID-19 (80%), IBD management (72%), and prevention measures (97%). Sixty-two percent of them showed moderate-high level of anxiety. High education level was independently associated with high knowledge about clinical importance of COVID-19 (odds ratio [OR] 5, 95% confidence interval [CI] 1.49-16.6, p = 0.009) and older age (OR 1, 95%, CI 1.01-1.1, p = 0.01), while the receipt of e-format educational material with low knowledge about clinical importance of COVID-19 (OR 3, 95%, CI 1.08-9.3, p = 0.03). Displaying an active disease appeared to be independently associated with low knowledge of IBD management (OR 5.8, 95% CI 1.4-22.8, p = 0.01) and no variables other than an older age was independently associated with higher level of anxiety (OR 1.04, 95% CI 1.009-1.09, p = 0.01). Conclusions: High educational level and aging promote knowledge about clinical importance of COVID-19, while e-format educational material does not. Taken together with findings that an active disease status compromises knowledge of IBD management and the high level of anxiety related to increasing age, these data suggest the need of further supporting patient-oriented strategies in IBD during Covid-19 pandemic.

A three-dimensional computed model of ST segment abnormality in type 1 Brugada Pattern: A key role of right ventricular outflow tract orientation?

Since its first description, Brugada Syndrome is characterized by definite ECG abnormalities (J wave, elevated ST segment) confined in right precordial leads. Brugada Pattern (BP) could be found in one or more right precordial leads, at conventional or higher intercostal spaces. A recent study, conducted by our group, reported that slightly less than one half of patients with type 1 BP show a definite ST segment depression (≥0.1 mV with duration ≥ 0.08 s) in the inferior leads. With these premises, 4 distinct ST abnormalities phenotypes can be recognizable in Type 1 BP. We speculated the key role of orientation of right ventricular outflow tract in the thorax, particularly the inclination of anterior wall compared to the sternum, contributing to the determination of these various ECG phenotypes. An interactive program, ECGsim, able to simulate ECG appearance in several anatomical and electrical models, confirmed this assumption. This computed model affirmed the strict relationship between ST segment depression in the inferior leads and the ST segment elevation in right precordial leads, typical of type 1 BP. A horizontal right ventricular outflow tract, in fact, gives raise to abnormal BP vector directed both superiorly and anteriorly, explaining, at the same time, typical BP appearance in right precordial leads and ST segment depression in the inferior leads.

Olive Tree Biophenols in Inflammatory Bowel Disease: When Bitter is Better.

The current therapeutic scenario for inflammatory bowel diseases (IBD) involves aminosalicylates, corticosteroids, and immunomodulators, but concerns regarding their safety profiles and high costs heavily impact their widespread use. In recent years, the beneficial effects thatbiophenols-from fruit and vegetables-have on human health have been investigated. The antioxidant and anti-inflammatory properties of phenolic fraction, from olive leaves and fruits, have been suggested, and a potential application in gut inflammation has been supported by in vitro and IBD-animal models studies. In the present review, we first introduced the potential therapeutic role of olive tree biophenolsin chronic inflammatory disease. Then, we aimed to describe their most interesting application for gut inflammation, as the results of basic science studies and animal experimental models. Finally, the potential role of olive tree biophenols in the setting of human IBD is discussed.

Self-Prescribed Dietary Restrictions are Common in Inflammatory Bowel Disease Patients and Are Associated with Low Bone Mineralization.

Background and objectives: Despite the serious concerns of patients about the role of food in triggering or ameliorating their intestinal disease, there are few studies dealing with patients' beliefs and practices regarding diet in inflammatory bowel disease (IBD). The aim of this study was to investigate how the disease affected the dietary habits of patients with IBD, and to assess if patients' food restrictions were responsible for low bone mineralization. Materials and Methods: For this study, 90 consecutive patients referred for IBD were interviewed regarding their dietary habits. Demographic features and clinical characteristics potentially associated with the dietary habits were collected. A validated and self-administered survey questionnaire dealing with dietary habits and patients' beliefs and perceptions regarding food was analyzed. Multivariate logistic regression analysis was performed in order to identify risk factors for dietary restrictions among participants and to evaluate the relationship between dietary restrictions and low bone mineral density (BMD). Results: Among the 63 (70%) patients who claimed a self-prescribed dietary restriction, 84% avoided dairy products. Significant risk factors (adjusted odds ratio (OR), 95% confidence interval (CI)) for the dietary restrictions were a younger age (p = 0.02), a higher level of education (p = 0.007), and a higher visceral sensitivity index (p = 0.009). Most (80%) of the patients displayed an inadequate calcium intake, and an abnormal result at dual-energy X-ray absorptiometry (DXA) scan accounting for low BMD was reported in 46 (51%) of them. Dietary restrictions (p = 0.03), and in particular avoiding dairy products(p = 0.001), were significant risk factors for a low BMD, along with female gender (p = 0.001), smoking(p = 0.04), and steroid abuse (p = 0.03). Almost all (86%) patients changed their diet after IBD diagnosis, as 8% believed that foods could have been a trigger for IBD and 37% that a proper diet was more important than drugs in controlling disease. Although 61% of the patients claimed to have received nutritional advice, 78% of the participants showed interest in receiving more. Conclusions: Dietary habits of IBD patients should be investigated by healthcare professionals as part of the routine visit. Clinicians are invited to provide nutritional recommendations to these patients in order to avoid unnecessary self-prescribed dietary restrictions.

Use of Complementary and Alternative Medicine by Patients with Irritable Bowel Syndrome According to the Roma IV Criteria: A Single-Center Italian Survey.

Aim: This study was conducted to evaluate the impact of complementary and alternative medicine (CAM) in patients with irritable bowel syndrome (IBS) as assessed by the Rome IV criteria. Methods: Consecutive patients referring for IBS were re-evaluated according to the Rome IV criteria. Demographic features and characteristics potentially associated with the use of CAM were collected. A validated, self-administered, survey questionnaire dealing with CAM and patients' level of knowledge, motivation, perception, and information seeking-behavior toward the use of CAM was analyzed. Multivariate logistic regression analysis was performed in order to identify predictors of CAM use among participants. Results: Among 156 patients claiming IBS, 137 (88%) met the Rome IV criteria, and 62 of them (45%) were CAM users. Biologically based therapy was the most chosen CAM (78%). Significant risk factors (adjusted odds ratio, 95% confidence interval) for the use of CAM were female gender (7.22, 2.31⁻22.51), a higher BMI (1.16, 1.02⁻1.33), and a good knowledge of CAM (4.46, 1.73⁻11.45), while having children was a protective factor (0.25, 0.07⁻0.95). Only 19% of patients used CAM due to medical advice and over half (51%) thought it was a "more natural" approach. Although a minority of patients (16%) had full satisfaction from CAM, 81% of users would repeat the CAM experience for their IBS symptoms. Conclusions: The widespread use of CAM in IBS, the patients' belief in its safety, and their willingness to re-use it suggest that knowledge of health-care providers and patient education should be improved.

The Skin in Celiac Disease Patients: The Other Side of the Coin.

Celiac disease (CD) is an autoimmune enteropathy that primarily affects the small intestine and is characterized by atrophy of intestinal villi. The manifestations of the disease improve following a gluten-free diet (GFD). CD is associated with various extra-intestinal diseases. Several skin manifestations are described in CD patients. The present paper reviews all CD-associated skin diseases reported in the literature and tries to analyze the pathogenic mechanisms possibly involved in these associations. Different hypotheses have been proposed to explain the possible mechanisms involved in every association between CD and cutaneous manifestations. An abnormal small intestinal permeability seems to be implicated in various dermatological manifestations. However, most of the associations between CD and cutaneous diseases is based on case reports and case series and a few controlled studies. To better assess the real involvement of the cutaneous district in CD patients, large multicentric controlled clinical trials are required.

Correlation between Thiopurine S-Methyltransferase Genotype and Adverse Events in Inflammatory Bowel Disease Patients.

Background and Objectives: In patients with inflammatory bowel diseases (IBD), the use of azathioprine results in adverse events at a rate of 5% to 20%. The aim of the study was to assess a possible correlation between genetic variability of the enzyme thiopurine S-methyltransferase (TPMT) and the development of toxicity to azathioprine. Materials and Methods: A retrospective, single center, blind, case-control study was conducted on 200 IBD patients, of whom 60 cases suspended azathioprine due to toxicity (leukopenia, pancreatitis, hepatitis, and nausea or vomiting), and 140 controls continued treatment with the drug without adverse events. Results: In the entire cohort, only 8 cases of heterozygous mutations of TPMT were observed, corresponding to 4% mutated haplotype rate, much lower than that reported in literature (close to 10%). No homozygous mutation was found. Regarding the TPMT allelic variants, we did not find any statistically significant difference between patients who tolerated azathioprine and those who suffered from adverse events. (OR = 0.77, 95% CI = 0.08-7.72; p = 0.82). Conclusions: According to our study, in IBD patients, the search for TPMT gene mutations before starting treatment with azathioprine is not helpful in predicting the occurrence of adverse events. Importantly, patients with allelic variants should not be denied the therapeutic option of azathioprine, as they may tolerate this drug.

Spike on T wave! What went wrong?

An 80-year-old male, who previously received a dual chamber pacemaker, was referred to our ambulatory for dizziness and fatigue. The ECG obtained showed sinus rhythm, highly variable atrioventricular (AV) interval and alternation between spontaneous and paced ventricular complexes. A spike on the ascending part of the T wave was observed, suggesting ventricular undersensing. However, telemetry-supported pacemaker control showed inconstant atrial undersensing.

SafeR and escape junctional rhythm: A singular trigger for pacemaker-mediated tachycardia.

A 70-year-old man, who previously received a dual chamber pacemaker for paroxysmal AV block (Sorin Symphony DR 2550), was noted on telemetry to have multiple episodes of rapid ventricular pacing at approximately 120bpm. Evaluation of the telemetry strips revealed that all of the rapid ventricular pacing episodes were initiated by brief runs of escape junctional rhythm. Programmed bradycardia parameters were AAI SafeR with lower rate limit of 50bpm.

A Case of Brugada Pattern Migrant from Right Precordial Leads to Peripheral Leads.

Since the first report in 1992, Brugada pattern (BP) diagnosis is mainly based on analysis of the precordial leads. In cases with no clear BP evidence in the conventional right precordial leads (4th intercostal space), limb leads analysis resulted helpful in suspecting BP. Fluctuations within right precordial leads between the diagnostic ECG pattern and nondiagnostic ECGs are well known. For the first time, in the patient herewith reported, the transformation of BP phenotype involves both precordial and peripheral leads, confirming that the analysis of all the 12 leads has a key role in BP diagnosis.

Tracking preference as unusual trigger of pacemaker-mediated tachycardia in a resynchronization device.

A 59-year-old woman with a history of congestive heart failure, who previously received a biventricular cardioverter-defibrillator was admitted with dyspnea and peripheral edema. She was noted on telemetry to have multiple self-terminated episodes of rapid ventricular pacing, consistent with pacemaker-mediated tachycardia. All episodes started after three consecutive ventricular extrasystoles. "Tracking preference" algorithm, designed to maintain atrial-tracked biventricular pacing in CRT devices, resulted turned on. It affected minimum PVARP and resulted the trigger for pacemaker mediated tachycardia.

Enhanced expression of indoleamine 2,3-dioxygenase in Helicobacter pylori-infected human gastric mucosa modulates Th1/Th2 pathway and interleukin 17 production.

BACKGROUND: Indoleamine 2,3 dioxygenase (IDO) interferes with immune responses. Host immune response against Helicobacter pylori is involved in the persistence of the infection and its related diseases. AIM: To investigate the role of IDO in the regulation of Th1/Th2 and Th17 pathways in H. pylori infection. METHODS: Gastric biopsy samples were taken from 42 patients who underwent endoscopy and evaluated for the expression of IDO by Western blotting. Gastritis was assessed by the Sydney system score. In a subgroup of patients, biopsies were treated with the IDO inhibitor 1-methyl-L-tryptophan and the expression of interferon-γ (IFN-γ) mRNA and that of T-bet, interleukin-17 (IL-17), and IL-4 determined by real-time PCR and Western blotting, respectively. RESULTS: IDO expression was found to be enhanced (p = .001) in gastric biopsies from H. pylori-infected (n = 18) compared with uninfected (n = 24) patients. Levels of IDO expression were inversely related to the gastritis score (r = -.684, p = .002) in H. pylori-infected gastric mucosa, but not in uninfected mucosa. In gastric biopsy cultures, IDO inhibition increased the expression of IFN-γ mRNA (p = .014), T-bet (p = .045), and IL-17 (p = .02) while decreasing that of IL-4 (p = .048). CONCLUSIONS: In H. pylori-infected human gastric mucosa, an enhanced expression of IDO is capable of modulating Th1/Th2 and Th17 pathways. This mechanism lowers gastric inflammation, possibly contributing to the persistence of H. pylori. Targeting the IDO pathway may be a new strategy for modulating H. pylori-induced mucosal immune response.