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This study aimed to collect and analyze the literature data regarding Chiari network (CN) and other right atrium (RA) remnants comprising the Eustachian and Thebesian valves (EV, ThV) as a potential entrapment site during different percutaneous cardiac procedures (PCP).A systematic search was conducted using Pubmed and Embase databases following the PRISMA guidelines to obtain available data concerning PCP associated with entrapment of inserted materials within CN-EV-ThV. The final analysis included 41 patients who underwent PCP with reported material entrapment within these RA remnants. The PCP was atrial septal defect (ASD)/patent foramen ovale (PFO) closure, catheter ablation, and pacemaker/defibrillator implantation in 44%, 22%, and 17% of patients, respectively. The entrapped materials were ASD/PFO devices, multipolar electrophysiology catheters, passive-fixation pacing leads, and J-guidewires in about 30%, 20%, 15%, and 10% of patients, respectively. Intraprocedural transthoracic, transoesophageal and intracardiac echocardiography showed sensitivity to reveal these structures of 20%, ∼95%, and 100%, respectively. A percutaneous approach successfully managed 70% of patients, while cardiovascular surgery was required in 20% and three patients died (7.3%).CN and other RA remnants may cause entrapment of various devices or catheters during PCP requiring right heart access. The percutaneous approach, guided by intraprocedural imaging, appears safe and effective in managing most patients. Prevention includes recognizing these anatomical structures at baseline cardiac imaging and intraprocedural precautions. Further studies are needed to analyze the actual incidence of this condition, its clinical impact and appropriate management.

Pulmonary artery pulsatility index (PAPi) is an indicator of right ventricular (RV) function and an independent predictor of right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation. Administration of vasodilator challenge during right heart catheterization (RHC) could reduce RV workload allowing a better assessment of its functional reserve. Patients undergoing LVAD implantation at our Institution between May 2013 and August 2021 were enrolled. Only patients who had undergone RHC and vasodilator challenge with sodium nitroprusside were analyzed. We collected all available clinical, instrumental, and haemodynamic parameters, at baseline and after nitroprusside infusion and evaluated potential associations with post-LVAD RVF. Of the 54 patients analyzed, 19 (35%) developed RVF after LVAD implantation. Fractional area change (FAC) (OR: 0.647, CI: 0.481–0.871; P = 0.004), pulmonary artery systolic pressure (PASP)(OR: 0.856, CI: 0.761–0.964; P=0.010), and post-sodium nitroprusside (NTP) PAPi (OR: 0.218, CI: 0.073–0.653; P = 0.006) were independent predictors of post-LVAD RVF. The model combining FAC, PASP, and post-NTP PAPi demonstrated a predictive accuracy of 90.7%. Addition of post-NTP PAPi significantly increased the predictive accuracy of the European Registry for Patients with Mechanical Circulatory Support right-sided heart failure risk score [79.4 vs. 70.4%; area under the curve (AUC): 0.841 vs. 0.724, P = 0.022] and the CRITT score (79.6% vs. 74%; AUC: 0.861 vs. 0.767 P = 0.033). Post-NTP PAPi has observed to be an independent predictor of RVF following LVAD implantation. Dynamic assessment of PAPi using a vasodilator challenge may represent a method of testing RV functional reserve in candidates for LVAD implantation. Larger and prospective studies are needed to confirm this hypothesis.

Introduction Class IC antiarrhythmic drugs (AADs) currently represent a cornerstone in the therapy of atrial fibrillation (AF). They also play an important role in the treatment of idiopathic ventricular arrhythmias. Following the results of the CAST study flecainide and by extension the other class IC AADs were contraindicated in patients with ischemic and structural heart disease, because of their proarrhythmic effect and the consequent increase in mortality observed in the study. Recent studies, carried out on patients with chronic coronary heart disease, have shown a good safety profile for this class of drugs. Methods The aim of our study was to evaluate the mortality and the mortality rate in patients affected by ischaemic heart disease who take Class IC AADs. A systematic review and meta-analysis was conducted using Pubmed and Embase databases, following the PRISMA guidelines, to collect literature data reporting Class IC AADs safety in patients affected by coronary artery disease. Results The final analysis included four studies accounting for a total of 3643. In the Classe IC AADs group the events (all cause death) were observed in 104/1170 patients, while in the control group were observed in 338/2473 patients, showing an ODDS ratio of 1.431 (IC 0.748-2.740), p value 0.279 (TABLE 1A). The event rate per year was 5,5% in the CLASS IC AADs group and 5,1 in the control group, with an ODDS ratio of 1.524 (IC 0.807-2.879), p value 0.194 (TABLE 1B). Conclusion Class IC AADs doesn't increase the overall mortality and mortality rate in patient affected by icheamic heart disease. These observations await confirmation through randomised clinical trial.

Introduction Systemic Sclerosis (SSc) is an autoimmune disease characterized by microvascular damage, immune system dysregulation and fibrosis of skin and internal organs. It is reported that asymptomatic involvement of the heart was found in 70% of SSc patients. The role of biomarkers in the early detection of fibrosis and vascular damage in SSc is not yet completely defined. Serum levels of sST2, Galectin 3, ANP, IL6 are a potential marker of cardiac involvement. In patients with chronic heart failure elevated levels of galectin-3 (>17.8 ng/ml) are a marker of worse prognosis. Moreover, a previous study reported a possible role of galectin-3 as an independent predictor of all-cause and cardiovascular mortality in SSc. Material and Methods We enrolled 62 SSc patients (53 females, median age 52 years) who fulfilled inclusion criteria. 35 patients had limited cutaneous SSc and 27 diffuse cutaneous SSc. 30 Healthy Controls (HC) were also enrolled [20 females; median age 50 years]. All SSc patients had normal echocardiographic and cardiac MRI findings. Results In SSc patients, the median Galectin value was 16.7 ng/ml, significantly higher than HC median (10,7 ng/Ml). sST2 and IL-6 median value was 30 ng/mL and 12,3 pg/mL respectively, which resulted significantly higher than the median value of HC patient (21,55 ng/mL and 4,5 pg/mL respectively). Therefore, there was a significant difference in biomarkers levels in the SSc group compared with controls. Conclusion These data suggest that these biomarkers can help identify a subgroup of SSc patients, with normal echocardiographic and RMN findings, who are at risk of developing heart involvement. In fact, all patients are scheduled for yearly echocardiographic re-evaluation as ESC guidelines recommend for earlier detection of pulmonary arterial hypertension (PAH), a leading cause of death in systemic sclerosis (SSc).

Introduction Pulmonary arterial hypertension (PAH) is a rare form of pulmonary hypertension (PH) that may also be associated with connective tissue diseases (CTD). In particular, PAH may affect from 5 to 19% of patients with systemic sclerosis (SSc), leading to a significant prognostic worsening. The current challenge is an early detection of PAH in such patients, in order to provide an early referral to PH centers to supply specific therapies as soon as possible. In the latest ESC guidelines for PH, cardiopulmonary exercise testing (CPET) has been included in the diagnostic algorithm for patients with unexplained exertional dyspnoea and/or suspected PH. Patients with PAH show a typical pattern, with a low end-tidal partial pressure of carbon dioxide (PETCO2), high ventilatory equivalent for carbon dioxide (VE/VCO2), low oxygen pulse (VO2/ HR) and low peak oxygen uptake (VO2). CPET may identify patients with SSc at low risk of PAH, to avoid unnecessary right heart catheterization (RHC). However, CPET is not available in all centers. So, we designed a preliminary study to identify new biomarkers that correlate with CPET's parameters. Material and Methods We enrolled 62 SSc patients [53 females, median age 52 years] with no other comorbidities and asymptomatic for dyspnea or other symptoms. 56% and 44% of them presented limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), respectively. For all patients we performed serum analysis for sST2, Galectine-3, pro-ANP, BNP and IL6, diagnostic imaging with echocardiography and cardiac MRI, CPET and pulmonary functionality test (PFT). Results All patients presented normal echocardiographic and RMI imaging findings. Galectin-3, sST2, pro-ANP, BNP and IL6 presented respectively the following median value: 13.45 ng/mL [11.78; 18.70], 23.25 ng/mL [13.04; 43.35], 1897 fmol/ml [1487; 2445], 12.18 pg/mL [9.34; 15.01]. Both Galectin-3 and sST2 showed a linear correlation with VE/VCO2 slope with R 0.339 (P-value 0.018) and 0.355 (P-value 0.013) respectively. After linear regression analysis, Galectin-3 and sST2 were overall statistically significant with R2 of 0.115 and 0.126, F of 5.97 and 6.62 and P-value of 0.018 and 0.013, respectively. It was found that Galectin-3 and SST2 significantly predicted VE/VCO2 slope with β = 0.364 [0,064; 0,665] for Galectin-3 and 0.137 [0,030; 0,244] for SST2. All other CPET parameters did not show correlation with the biomarkers. Conclusion Our preliminary results suggest that Galectine-3 and sST2 may be useful biomarkers for predicting increasing VE/VCO2 slope. Future analysis may confirm the role of these new biomarkers for early detection of pulmonary vascular involvement in SSc patients to allow an early referral and treatment and, conversely, to avoid unnecessary RHC.

The role of Lipoprotein(a) (Lp[a]) in risk stratification following an acute myocardial infarction (AMI) is still debated. We aimed to investigate whether elevated Lp(a) levels in patients with AMI treated by percutaneous coronary intervention (PCI) are associated with worse outcomes.We designed a retrospective registry including patients with AMI undergoing PCI. The occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as death from cardiovascular causes, recurrent myocardial infarction, unplanned coronary revascularization and stroke, was assessed at follow up and compared between patients with high (≥ 30 mg/dl) and low (30 mg/dl) Lp(a) levels. Cox proportional hazard analysis was performed in order to assess independent predictors of MACCE.During a 3-year period (2018-2020) we identified 634 patients with AMI treated by PCI and known Lp(a) blood levels; follow up visits were performed in 414 patients (median length 29 months [19-38]). Median Lp(a) level was 18 mg/dl [8-42]. The incidence of MACCE was significantly higher in high as compared to low Lp(a) group (log-rank p=0.018). The following independent predictors were identified at multivariate Cox regression: Lp(a) ≥30 mg/dl (HR 1.82 [95% CI 1.04-3.19], peripheral artery disease (HR 4.62 [95% CI 2.50-8.54]), number of diseased coronary vessels (HR 1.51 [95% 1.03-2.24] and presence of a coronary chronic total occlusion at coronary angiography (HR 3.46 [95% CI 1.77-6.76]).In this study, Lp(a) values ≥30 mg/dl were associated to worse outcomes in patients with AMI receiving PCI. Lp(a) could represent a useful tool to identify patients at high risk of recurrent events.

To evaluate the clinical outcomes of oral mexiletine (oMXT) to treat ventricular tachyarrhythmias (VTAs) in the era of implantable cardioverter-defibrillator (ICD) technology.A systematic search was conducted using Pubmed, Embase and Cochrane databases following the PRISMA guidelines to collect literature data reporting oMXT efficacy and safety outcomes in treating VTAs in ICD recipients.Final analysis included four studies accounting for a total of 91 patients with recurrent VTAs treated with oMXT. Amiodarone therapy was initially attempted in most patients (91.2%), while catheter ablation was performed in one-third of patients. VTA recurrences were observed in 55/91 patients (60.4%) during oMXT treatment compared to 91/91 (100%) before treatment (p0.001). Appropriate therapies occurred in 55/88 ICD patients (62.5%) during oMXT treatment compared to 80/88 (90.9%) before treatment (p0.001). After oMXT introduction, there was a significant reduction of the individual burden of VTA episodes and appropriate ICD therapies per patient, showing Hedges'g values of -1.103 (p = 0.002) and -1.474 (p = 0.008), respectively. Safety analysis showed a sample-weighted overall side-effect rate of 30%, while 21% of patients required drug reduction or discontinuation. Aggregated meta-regression analysis of the included studies and remote literature revealed a linear correlation between oMXT dosage and the overall side effects rate (r2 = 0.48; p = 0.014).Oral mexiletine provides an adjunctive treatment to manage VTAs and reduces appropriate therapies in ICD patients with moderate efficacy and acceptable safety profiles. These observations await confirmation through randomised clinical trials.

Currently, few evidences have shown the possible involvement of autoimmunity in patients affected by coronavirus disease 2019 (COVID‐19). In this study, we elucidate whether severe acute respiratory syndrome coronavirus disease 2 (SARS‐CoV‐2) stimulates autoantibody production and contributes to autoimmunity activation. We enrolled 40 adult patients (66.8 years mean age) admitted to Alessandria Hospital between March and April 2020. All the patients had a confirmed COVID‐19 diagnosis and no previously clinical record of autoimmune disease. Forty blood donors were analyzed for the same markers and considered as healthy controls. Our patients had high levels of common inflammatory markers, such as C reactive protein, lactate dehydrogenase, ferritin, and creatinine. Interleukin‐6 concentrations were also increased, supporting the major role of this interleukin during COVID‐19 infection. Lymphocyte numbers were generally lower compared with healthy individuals. All the patients were also screened for the most common autoantibodies. We found a significant prevalence of antinuclear antibodies, antineutrophil cytoplasmic antibodies, and ASCA immunoglobulin A antibodies. We observed that patients having a de novo autoimmune response had the worst acute viral disease prognosis and outcome. Our results sustain the hypothesis that COVID‐19 infection correlates with the autoimmunity markers. Our study might help clinicians to: (a) better understand the heterogeneity of this pathology and (b) correctly evaluate COVID‐19 clinical manifestations. Our data explained why drugs used to treat autoimmune diseases may also be useful for SARS‐CoV‐2 infection. In addition, we highly recommend checking patients with COVID‐19 for autoimmunity markers, mainly when deciding on whether to treat them with plasma transfer therapy. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? ☑ Recent data sustain the idea that autoimmune phenomena exist in patients with coronavirus disease 2019 (COVID‐19), but other investigations are necessary to define the possible link between severe acute respiratory syndrome coronavirus disease 2 (SARS‐CoV‐2) infection and autoimmune disease onset. WHAT QUESTION DID THIS STUDY ADDRESS? ☑ In this monocentric study, we demonstrated how SARS‐CoV‐2 infection could be associated with an autoimmune response and development of autoantibodies. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? ☑ Patients with COVID‐19 having an increased level of inflammatory markers and strong autoantibodies positivity (i.e., antinuclear antibodies and antineutrophil cytoplasmic antibodies) presented the worst clinical outcome. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? ☑ These results suggest that the drugs normally used to treat autoimmune diseases should also be considered during SARS‐CoV‐2, improving public health. In addition, before starting a transfer plasma therapy, it is important to also evaluate the autoimmunity conditions of the patients with COVID‐19. Transferring antibodies or trying to neutralize them should be done with precaution. It is possible that the risk of developing or increasing the autoimmune response may enhance.

Hypertrophic cardiomyopathy (HCM) and Long QT Syndrome (LQTS) are inherited diseases characterized by a wide genetic heterogeneity. Based on the separate incidence of these pathologies and on the absence of linkage, the occurrence of both diseases in the same individual has an incidence of about 1/250000. We describe a rare case report of a 24 years-old patient with maternal familiarity for type 1 LQTS (mother carrier of KCNQ1 c.1781G>A) and paternal familiarity for HCM (father carrier of TNNI3 c.592C>G mutation) who inherited both gene mutations and was diagnosed with HCM and LQTS later in adolescence, after clinical and genetic evaluations.

Predictors of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) do not include ECG variables. Intrinsicoid deflection (ID) represents the early ventricular depolarization on surface ECG. Delayed ID (DID) has been associated with sudden cardiac arrest (SCA) in the community. In a cohort of consecutive patients with HCM, we assessed whether DID predicts SCA or its surrogates.We reviewed ECG, clinical and follow-up data of 344 consecutive HCM patients. DID (ID ≥50 ms) was classified as lateral (leads I or aVL), inferior (leads II, III or aVF), and precordial (leads V5 or V6). The endpoint was a combination of SCD, resuscitated SCA or appropriate ICD intervention.The SCA group was composed by 2 secondary prevention ICD recipients and 23 patients that reached the endpoint during follow-up (108 ± 73 months). SCA patients had more frequently massive LV hypertrophy (LVH) or end-stage HCM. ECG indexes of LVH were comparable between SCA and controls. SCA patients were more likely to have DID on ECG lateral leads I/aVL (72% vs 44%; p = 0.008). A non significant trend was observed for inferior and V5/V6 leads. DID I/aVL was associated with SCA in multivariate analysis after correction for massive LVH and end-stage disease (HR: 2.86; 95%CI: 1.14-7.13; p = 0.02).In HCM patients DID is associated with increased risk of SCA. Its prognostic value extends beyond that of LVH. If confirmed in prospective studies, the prognostic power of this ECG marker could be used to refine risk prediction.

Aims Pulmonary artery pulsatility index (PAPi) is an indicator of right ventricular (RV) function and an independent predictor of right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation. Administration of vasodilator challenge during right heart catheterization (RHC) could reduce RV workload allowing a better assessment of its functional reserve. Methods and results Patients undergoing LVAD implantation at our Institution between May 2013 and August 2021 were enrolled. Only patients who had undergone RHC and vasodilator challenge with sodium nitroprusside were analyzed. We collected all available clinical, instrumental, and haemodynamic parameters, at baseline and after nitroprusside infusion and evaluated potential associations with post-LVAD RVF. Of the 54 patients analyzed, 19 (35%) developed RVF after LVAD implantation. Fractional area change (FAC) (OR: 0.647, CI: 0.481–0.871; P = 0.004), pulmonary artery systolic pressure (PASP) (OR: 0.856, CI: 0.761–0.964; P = 0.010), and post-sodium nitroprusside (NTP) PAPi (OR: 0.218, CI: 0.073–0.653; P = 0.006) were independent predictors of post-LVAD RVF. The model combining FAC, PASP, and post-NTP PAPi demonstrated a predictive accuracy of 90.7%. Addition of post-NTP PAPi significantly increased the predictive accuracy of the European Registry for Patients with Mechanical Circulatory Support right-sided heart failure risk score [79.4 vs. 70.4%; area under the curve (AUC): 0.841 vs. 0.724, P = 0.022] and the CRITT score (79.6% vs. 74%; AUC: 0.861 vs. 0.767 P = 0.033). Conclusion Post-NTP PAPi has observed to be an independent predictor of RVF following LVAD implantation. Dynamic assessment of PAPi using a vasodilator challenge may represent a method of testing RV functional reserve in candidates for LVAD implantation. Larger and prospective studies are needed to confirm this hypothesis.

Abstract: Stroke is defined as an acute cerebrovascular accident characterized by an interruption of vascular supply lasting more than 24 hours. Therapeutic goal, reassumed at the well-known “time is brain”, is strictly focused on achieving timely restoration of cerebral blood flow at risk of infarction to reduce neurological complications. Consequently, time to treatment is the most important determinant of the efficacy of reperfusion. Current guidelines strongly recommend the use of intravenous thrombolysis with tissue plasminogen activator and endovascular thrombectomy to reach that goal. These therapies allow to obtain 1.9 million neurons saved per each minute of onset-to-reperfusion time and 4.2 days of extra healthy life and are crucial in the reduction of mortality and morbidity of ischemic stroke. Multidisciplinary collaboration involving a coordinated prehospital management and stroke team composed of physicians with expertise in emergency medicine, neurologists, radiologists, nurses, technicians, and laboratory personnel are essential for rapid triage and should guide clinical decisions to deliver the appropriate reperfusion therapy for each patient.

Aims Several randomized controlled trials (RCTs) consistently reported better clinical outcomes with radial as compared to femoral access for primary percutaneous coronary intervention (PCI). Nevertheless, heterogeneous use of potent antiplatelet drugs, such as Gp IIb/IIIa inhibitors (GPI), across different studies could have biased the results in favour of radial access. We performed an updated meta-analysis and meta-regression of RCTs in order to appraise whether the use of GPI had an impact on pooled estimates of clinical outcomes according to vascular access. Methods and results We computed pooled estimates by the random effects model for the following outcomes: mortality, major adverse cardiovascular events (death, myocardial infarction, stroke, and target vessel revascularization), and major bleedings. Additionally, we performed meta-regression analysis to investigate the impact of GPI use on pooled estimates of clinical outcomes. We analysed 14 randomized controlled trials and 11 090 patients who were treated by radial (5497) and femoral access (5593), respectively. Radial access was associated with better outcomes for mortality [risk difference 0.01 (0.00, 0.01), P = 0.03], MACE [risk difference 0.01 (0.00, 0.02), P = 0.003], and major bleedings [risk difference 0.01 (0.00, 0.02), P = 0.02]. At meta-regression, we observed a significant correlation of mortality with both GPI use (P = 0.011) and year of publication (P = 0.0073), whereas no correlation was observed with major bleedings. Conclusions In this meta-analysis, the use of radial access for primary PCI was associated with better clinical outcomes as compared to femoral access. However, the effect size on mortality was modulated by GPI rate, with greater benefit of radial access in studies with larger use of these drugs.

Papillary muscle rupture (PMR) is an infrequent but catastrophic complication after myocardial infarction (MI). Surgical procedure is considered the optimal treatment, despite high risk. However, the gold standard technique is still a major dilemma. Therefore, a meta-analysis was carried out to assess and provide an overview comparing mitral valve replacement (MVR) and mitral valve repair (MVr) for PMR post-MI.A systematic literature search was performed. Data were extracted and verified using a standardized data extraction form. Meta-analysis was realized mainly using RevMan 5.4 software.From four observational studies 1640 patients were identified; 81% underwent MVR and 19% MVr. Operative mortality results were significantly higher in MVR group than the MVr group. MVR was performed under emergency conditions and patients admitted in cardiogenic shock or who required the use of mechanical cardiac support underwent MVR. MVr had shorter time of hospitalization and similar incidence of postoperative complications than MVR. No significant differences existed between the two procedures regarding cardiopulmonary bypass time.Mitral valve repair appears to be a viable alternative to MVR for post-MI PMR, given that it has lower operative mortality, shorter time of hospitalization and similar incidence of short-term postoperative complications than MVR. However, it needs to be pointed out that MVR was associated with the most critical clinical condition following PMR. There is uncertainty regarding the overall survival and improvement of the quality of life between the procedures. Nevertheless, further completed investigation is required.

Objectives. Several randomized controlled trials (RCTs) consistently reported better clinical outcomes with radial as compared to femoral access for primary percutaneous coronary intervention (PCI). Nevertheless, heterogeneous use of potent antiplatelet drugs, such as Gp IIb/IIIa inhibitors (GPI), across different studies could have biased the results in favor of radial access. We performed an updated meta-analysis and meta-regression of RCTs in order to appraise whether the use of GPI had an impact on pooled estimates of clinical outcomes according to vascular access. Methods. We computed pooled estimates by the random-effects model for the following outcomes: mortality, major adverse cardiovascular events (death, myocardial infarction, stroke, and target vessel revascularization), and major bleedings. Additionally, we performed meta-regression analysis to investigate the impact of GPI use on pooled estimates of clinical outcomes. Results. We analyzed 14 randomized controlled trials and 11090 patients who were treated by radial (5497) and femoral access (5593), respectively. Radial access was associated with better outcomes for mortality (risk difference 0.01 (0.00, 0.01), p = 0.03 ), MACE (risk difference 0.01 (0.00, 0.02), p = 0.003 ), and major bleedings (risk difference 0.01 (0.00, 0.02), p = 0.02 ). At meta-regression, we observed a significant correlation of mortality with both GPI use ( p = 0.011 ) and year of publication ( p = 0.0073 ), whereas no correlation was observed with major bleedings. Conclusions. In this meta-analysis, the use of radial access for primary PCI was associated with better clinical outcomes as compared to femoral access. However, the effect size on mortality was modulated by GPI rate, with greater benefit of radial access in studies with larger use of these drugs.

Objective: The study evaluated the autoimmune profile of COVID-19 positive hospitalised patients. Methods: 40 hospitalised patients with a confirmed diagnosis of COVID-19 were given clinical chemistry and autoimmunity tests. Results: The 40 patients enrolled in our hospital had elevated levels of common inflammatory markers such as C-Reactive Protein (CRP), Lactate Dehydrogenase (LDH) and ferritin. Interleukin-6 (IL-6) concentration was also increased, confirming the key role of this interleukin during severe acute respiratory syndrome (SARS-CoV-2) infection. The most common autoimmunity tests were performed. A significant prevalence of anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and anti-Saccaromyces cerevisiae (ASCA IgA and IgG) was found. Patients showing a de novo autoantibody response were those with a worse disease prognosis. Conclusion: Our study shows that COVID-19 infection can trigger an autoimmune response and could induce the onset of autoimmune diseases. These data explain why drugs used to treat autoimmune diseases could also be useful in combating SARS-CoV-2 infection.

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

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

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

In the adult, the human intestine houses myriads of microorganisms, quantitatively up to 100 trillion and qualitatively over 500 species of bacteria, exceeding the number of host somatic cells by at least one order of magnitude. Actually, it remains a mystery as to how the intestine is able to contain such large quantities of bacteria without evident harm to the host. However, it is well known that a very complex symbiotic relationship between the intestinal microflora and the host insures mutual advantages for both partners. Despite the recent advances in immunology and microbiology, the possibility of studying human intestinal microflora is limited by great inter-individual variability and difficulties in creating standard conditions to uniform the samples. However, there are clinical conditions which are useful to explain the role of intestinal bacteria in the human gut. Small intestinal bacterial overgrowth (SIBO) is a good example, because this is a microbial alteration of intestinal microflora, in absence of pathogenic bacteria and severe dysregulation of the immune system. On the other hand, the pathogenesis and clinical aspects of SIBO could clarify the complex and bi-directional relationship between the microbiota and the host.

The best therapeutic approach for patients with small bowel bacterial overgrowth is a combination of the removal of all predisposing conditions and the administration of broad-spectrum antibiotics. In the case of non-modifiable predisposing factors, patients with bacterial overgrowth need a strict follow-up after successful decontamination with antibiotics, in order to promptly assess and treat disease recurrence. Up to now, the choice of antibiotics has been primarily empiric because of the presence of several different bacterial species in the contaminating flora and the impossibility of applying in vitro susceptibility tests. Several systemic and non-absorbable antibiotic agents have been shown to be effective for decontamination of small bowel bacterial overgrowth. The best antibiotic scheme in terms of drug, dosage and duration of therapy remains, however, to be assessed. The non-absorbable agents seem to be associated with better safety and tolerability than systemic drugs. In the present paper, all available therapeutic approaches to small bowel bacterial overgrowth are reviewed.

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

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

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

Portal Vein Tumor Thrombosis Revascularization During Sorafenib Treatment for Hepatocellular Carcinoma

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

Intestinal epithelium, mucosal immune system, and bacterial flora represent a morpho-functional system on dynamic balance responsible for the intestinal metabolic and trophic functions, and the regulation of mucosal and systemic host’s immunity. Obesity is a pathological condition affecting a growing number of people especially in the Western countries resulting from the failure of the organism’s energetic balance based on the perfect equality of income, waste, and storage. Recent evidences explain the mechanisms for the microbial regulation of the host’s metabolism both in health and disease. In particular, animal studies have explained how quali-/quantitative changes in microflora composition are able to affect the absorption of the nutrients and the energy distribution. Antibiotics, prebiotics, probiotics, and symbiotics are the instruments utilized in the current clinical practice to modulate the intestinal bacterial flora in man both in health and pathologic conditions with promising preliminary results on prevention and therapy of obesity and related metabolic diseases.

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

The epigastrium is the site where pain coming from both abdominal and extra-abdominal organs is frequently referred. Although acute or chronic diseases of the stomach, duodenum, liver, pancreas and biliary tree are the most common causes of acute epigastric pain, several other entities, potentially more severe, should also be suspected and investigated. Clinical bedside ultrasonography (US) is actually the first-line imaging in acute epigastric pain patients presenting to the hospital Emergency Department (ED) because it is rapid, noninvasive, relatively inexpensive and focused, repeatable and reliable. Moreover, the systematic use of emergency US as a complement to routine management might save economic resources by avoiding further costs for complications and substantially reducing the time for making an accurate diagnosis. The purpose of this paper is to review the US spectrum of the most common diseases responsible for acute epigastric pain onset. We also propose a focused, well codified US protocol, that we call the "$ approach", based on our clinical experience and the current literature for acute non-traumatic epigastric pain evaluation in an emergency setting. Its systematic application by the emergency physician may reduce the wait for diagnosis and the over-usage of second-line radiological techniques, including computed tomography, as well as to increase the diagnostic accuracy with potential benefits for patient (safety), physician (efficacy) and the institution (efficiency).

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

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

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

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