Single suture-mediated closure system after transfemoral transcatheter aortic valve implantation: A single-center real-world experience.

BACKGROUND: Despite the use of two crossed Perclose ProGlide™ (Abbott Vascular Devices) is the most widespread technique to close the main arterial access in transfemoral transcatheter aortic valve implantation (TF-TAVI), the safest and most effective strategy still remains much debated. AIMS: The aim of the present study was to evaluate the performance of a single Perclose ProGlide suture-mediated closure device to obtain femoral hemostasis after sheathless implantation of self-expanding transcatheter heart valves through their 14 F-equivalent fix delivery systems. METHODS: This prospective observational study included 439 patients undergoing TF-TAVI at the "Montevergine" Clinic of Mercogliano, Italy. All patients underwent hemostasis of the large-bore access using a single Perclose ProGlide with preclose technique, after sheathless implantation of self-expanding transcatheter heart valves through 14 F-equivalent fix delivery systems. A multidetector computed tomography analysis of size, tortuosity, atherosclerotic, and calcification burdens of the ilio-femoral access route was made by a dedicated corelab. Vascular complications (VCs), percutaneous closure device (PCD) failure, and bleedings were adjudicated by a clinical events committee. RESULTS: A total of 81 different VCs were observed in 60 patients (13.7%); among these, 41 (5% of patients) were categorized as major. PCD failure occurred in 14 patients (3.2%). At the logistic regression analysis, no predictors of PCD failure have been identified. CONCLUSION: This registry suggests that the use of a single suture-mediated closure device could be considered a safe and efficient technique to achieve access site hemostasis in patients undergoing TF-TAVI through 14 F-equivalent fix delivery systems.

Fluoroscopy Time as a New Predictor of Short-Term Outcomes after Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an almost totally cine-fluoroscopic guided procedure. The amount of radiation used during the procedure is strictly related to the fluoroscopy time (FT), that has already been demonstrated to be associated with outcomes and complexity of coronary procedures. The aim of our study is to demonstrate the relationship between FT and the short-term outcomes after TAVR defined by to the Valve Academic Research Consortium (VARC)-2 and -3 consensus documents. METHODS: After splitting 1797 consecutive patients into tertiles of FT, the composite endpoint early safety (ES) was adjudicated according to VARC-2 and VARC-3 definitions, whereas the composite endpoints device success (DS) and technical success (TS) according to VARC-3 criteria. RESULTS: The absence of all these outcomes (VARC-2 ES amd VARC-3 TS, DS, and ES) was significantly associated with longer FT: this association was independent from both intraprocedural complications and other intraprocedural factors linked to longer FT, and still persisted after propensity score matching analysis. Notwithstanding, after receiver operating characteristic analysis, FT had adequate diagnostic accuracy in identifying the absence of only VARC-3 TS and VARC-2 ES. CONCLUSION: Longer FT is related with periprocedural and short-term outcomes after the procedure, especially in those that are more challenging. A FT duration of more than 30 min has an adequate accuracy in identifying VARC-3 technical failure (TS and DS) and absence of VARC-2 ES, selecting patients who are likely to take advantage from more careful in-hospital follow-up.

Surgical Mortality Risk Scores in Transcatheter Aortic Valve Implantation: Is Their Early Predictive Value Still Strong?

BACKGROUND: Surgical mortality risk scores, even if not properly designed and rarely tested in the transcatheter aortic valve implantation (TAVI) setting, still guide the heart team in managing significant aortic stenosis. METHODS: After splitting 1763 consecutive patients retrospectively based on their mortality risk thresholds, the composite endpoint early safety (ES) was adjudicated according to Valve Academic Research Consortium (VARC)-2 and -3 consensus documents. RESULTS: ES incidence was higher if VARC-2 rather than VARC-3 defined. Despite only patients showing VARC-2 ES had significantly lower absolute values of all three main risk scores, these last still failed to foresee both VARC-2 and -3 ES in intermediate-risk patients. The receiver operating characteristic analysis also showed a significant correlation, but with poor diagnostic accuracy, among the three scores and only VARC-2 ES; moreover, the absence of VARC-2 ES and low-osmolar contrast media administration were identified as independent predictors of 1-year mortality and absence of VARC-3 ES, respectively. Finally, even a single complication included in the ES definition could significantly affect 1-year mortality. CONCLUSION: Currently, the most used mortality risk scores do not have adequate diagnostic accuracy in predicting ES after TAVI. The absence of VARC-2, instead of VARC-3, ES is an independent predictor of 1-year mortality.

Efficacy of a new nutraceutical formulation: L-tryptophan, probiotics, charcoal, chamomile, mint, and licorice (COLONIR®) in the improvement of gastrointestinal symptoms in subjects with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. IBS is characterized by recurrent chronic abdominal pain and altered bowel habits in the absence of organic damage. Although there are reviews and guidelines for treating IBS, the complexity and diversity of IBS presentation make treatment difficult. Treatment of IBS focuses on relieving symptoms as mild signs and symptoms can often be controlled by managing stress and by making changes in diet and lifestyle. The use of nutraceutical compounds has been advocated as a possible alternative treatment in patients with IBS. COLONIR® (Omega Pharma Srl, Milan, Italy) may be an alternative or adjuvant treatment in patients with gastrointestinal symptoms. This study aimed to evaluate the effect of this new nutraceutical formulation in inducing symptoms remission and improve gastrointestinal habits. METHODS: An initial cohort of 1004 consecutive patients referred to 25 different Units of Internal Medicine a/o Gastroenterology in Italy to perform colonoscopy for intestinal symptoms was asked to participate. Patients were treated for 2 months with two doses of nutraceuticals/day during meals namely COLONIR®. Patients were assessed at baseline and after 2 months to evaluate the frequency and severity of gastrointestinal symptoms in the past seven days with a questionnaire based on ROMA IV criteria. RESULTS: After 2 months, 899 patients completed the follow-up. COLONIR® achieved a statistically significant reduction of severity of symptoms in the study population without any documented side effects. CONCLUSIONS: These promising results, here reported, need to be confirmed, valuating the efficacy of COLONIR® in relieving gastrointestinal symptoms in IBS patients in further studies.

Early acute kidney injury after transcatheter aortic valve implantation: predictive value of currently available risk scores.

BACKGROUND: Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is a frequent complication associated with adverse outcomes and mortality. Various scores have been developed to predict this complication in the coronary setting. However, none have ever been tested in a large TAVI population. This study aimed to evaluate the power of four different scores in predicting AKI after TAVI. METHODS: Overall, 1535 consecutive TAVI patients from the observational multicentric "Magna Graecia" TAVI registry were included in the analysis. Of the study population, 235 (15.31%) developed AKI early. The Mehran, William Beaumont Hospital, CR4EATME3AD3, and ACEF scores were calculated retrospectively. RESULTS: The patients who developed TAVI-related AKI had significantly higher absolute values of all risk scores than those who did not. The receiver-operating characteristic analysis also showed a significant correlation between these four scores and AKI, but without a significant difference among all of them (p value = 0.176). Nevertheless, based on their area under the curve values (≤0.604 for all), none had adequate diagnostic accuracy in predicting TAVI-related AKI. Importantly, multivariate analysis identified myocardial revascularization close to the TAVI procedure and implantation of self-expanding prostheses, as well as atrial fibrillation, low-osmolar contrast media administration, corrected contrast medium volume, and any transfusion (p value < 0.05 for all) as independent risk factors for AKI. CONCLUSIONS: Although high values of current AKI risk scores are significantly associated with the development of this complication, these are not sufficiently accurate. Further studies are needed so that a TAVI-dedicated AKI risk score may be created.

Three-year outcome of directional atherectomy and drug coated balloon for the treatment of common femoral artery steno-occlusive lesions.

BACKGROUND: Endarterectomy is considered the gold standard therapy for common femoral artery (CFA) steno-occlusive lesions, but a significant risk of perioperative mortality and complications has been reported. OBJECTIVE: Aim of this study is to evaluate the efficacy at a long-term follow-up of patients with CFA steno-occlusive lesions treated with directional atherectomy and drug coated balloon (DCB). MATERIAL AND METHODS: In this single-center registry, 78 patients (male: 80.7%; age: 71 ± 15 years; occlusions: 25%) with 80 CFA lesions were included, with 39.7% of them undergoing directional atherectomy and drug coated balloon due to critical limb ischemia and 60.3% due to lower-limb intermittent claudication. The long-term follow-up was completed by 75 patients (3 years). The 31 patients with critical ischemia (39.7%) were further subdivided into 20 (25.6%) patients with pain at rest and 11 (14.1%) with trophic changes, ulcers and/or tissue loss. We considered the primary and the secondary outcome, referring, respectively to peak systolic velocity ratio (PSVR) ≥ 2.4 on duplex or > 50% stenosis on digital subtraction angiography at 36 months and to clinically driven target lesion revascularization at 36 months. RESULTS: The primary and secondary outcome was obtained in 84% and 86.7% of patients, at 36 months of follow up. Bailout stenting was necessary in 6/80 cases (7.5%) for suboptimal result. Freedom from MALE was obtained in 98.6% of patients. CONCLUSIONS: These results confirm that directional atherectomy and drug coated balloon strategy for the treatment of CFA lesions is effective at a long-term follow-up and could be considered as a good alternative to surgery.

Evaluation of Antibiotic Resistance of Helicobacter pylori Strains Isolated in Bari, Southern Italy, in 2017-2018 by Phenotypic and Genotyping Methods.

Objective: Helicobacter pylori antibiotic resistance is a constantly evolving process and local surveillance is warranted to guide clinicians in the choice of therapy. Materials and Methods: Antibiotic susceptibility testing was performed by E-test on 92 H. pylori strains, and resistance to clarithromycin and levofloxacin was also evaluated using a commercially available genotyping method. Results: In naïve patients the resistance to clarithromycin, levofloxacin, and metronidazole was 37.7%, 26.2%, and 16.4%, respectively, significantly lower than the percentage found in treated patients. Concomitant resistance to ≥2 antibiotics was also observed in naïve patients. The A2143G mutation of the 23S-rRNA gene was the most frequently detected, also in naïve patients. The highest minimum inhibitory concentration (MIC)50 value (256 mg/L) was associated with A2142 mutations in all the patients carrying them. For levofloxacin resistance a mutation in codon 87 was detected in 63.9% and in codon 91 in 36.1% of the H. pylori strains, without significant differences in the patients groups. A mutation in codon 87 was associated with the highest MIC50 value (32 mg/L). Conclusions: In our area, a high prevalence of H. pylori primary resistance was detected; these rates were higher in patients who had experienced failure of several courses of therapy. A better knowledge of the local epidemiology of resistance, and the genotypes responsible, will improve the H. pylori eradication rates.

Cardiogenic Shock Following Acute Myocardial Infarction: What's New?

Cardiogenic shock (CS) is a state of critical end-organ hypoperfusion primarily due to cardiac dysfunction. This condition is the most common cause of death in patients affected by acute myocardial infarction (AMI). Despite early revascularization, prompt optimal medical therapy, and up-to-date mechanical circulatory supports, mortality of patients with CS remains high.The objective of this review is to summarize epidemiology, pathophysiology, and treatment options of CS in light of the new European Society of Cardiology (ESC) recommendations. The latest European guidelines on myocardial revascularization have reviewed the previous guidelines with respect to early multivessel revascularization and routine use of intra-aortic balloon pump (IABP) in patients with AMI-related CS.Most of the current evidences come partly from randomized trials, but mostly from observational registries because of the difficulty to test different treatments in this life-threatening clinical setting.Some of the latest studies highlight the potential crucial benefit of newly introduced mechanical circulatory support devices, although evidences are not sufficient to definitely assess the benefit/risk ratio of the different systems.Many questions remain unanswered in this field, and further trials are advocated to better elucidate the best medical, reperfusion, and circulatory support approaches aimed to improve the poor prognosis of patients with CS after AMI.

Administration Timing Is the Best Clinical Outcome Predictor for Adalimumab Administration in Crohn's Disease.

Biological intervention for Crohn's Disease (CDs) patients, mainly using anti-TNF antibodies, is often an efficient therapeutic solution. Nonetheless, data defining the administration timing to maximize the chances of clinical remission are lacking. The objective of this "real-life" retrospective study was to evaluate if early Adalimumab (ADA) administration (<12 months) was an efficient strategy to improve patients' clinical outcome. This single center study included 157 CD patients, of which 80 received the first ADA administration within the first 12 months from the diagnosis. After 1 year of therapy, clinical remission was observed in 50.32% of patients, mucosal healing in 37.58%. Clinical remission was observed in 66.25% of the early ADA administration patients vs. 33.77% of the late (>12 months) (p < 0.001); mucosal healing was observed in 53.75% of the early vs. 20.78% of the late (p < 0.001). Dose escalation was required for 30.00% of the early vs. 66.23% of the late (<0.01). In the early ADA administration group, 7.50% patients were considered non-responders at the end of the follow-up vs. 22.08% patients in the late administration group. These findings highlighted that early ADA administration (within 1 year of diagnosis) improves the clinical response and mucosal healing, and reduces the loss of response rate and need for dose escalation.

Prevalence of primary clarithromycin resistance in Helicobacter pylori strains over a 15 year period in Italy.

OBJECTIVES: The frequency of primary clarithromycin resistance in Helicobacter pylori strains is increasing worldwide, and its presence significantly reduces the treatment efficacy of infection. This study aimed to evaluate whether the progression of the prevalence of clarithromycin resistance over a 15 year period has increased and whether a possible change in the distribution of the three most frequent point mutations, which account for the large majority of clarithromycin resistance cases, has taken place. METHODS: Antral biopsies of consecutive H. pylori-positive patients observed between January 1989 and December 1990 and between January 2004 and December 2005 were retrieved. A TaqMan real-time PCR was performed in all cases to assess point mutations involved. RESULTS: Primary clarithromycin resistance was assessed for 147 patients observed in the first period 1989-90 and 178 cases observed in the second period 2004-05. The overall frequency of clarithromycin resistance increased from 10.2% (15 patients) to 21.3% (38 patients) during the study period (P = 0.01). The increase was more evident in females [4 out of 55 patients (7.2%) versus 24 out of 103 patients (23.3%); P = 0.01] and in non-ulcer dyspepsia patients [13 out of 106 patients (12.2%) versus 37 out of 140 (26.4%) patients; P = 0.009]. A2143G was the most frequent point mutation observed in both study periods, and its prevalence rate remained unchanged [11 out of 15 (73.3%) patients versus 27 out of 38 (71%) patients; P = 1]. CONCLUSIONS: A 2-fold increase in primary clarithromycin resistance in H. pylori strains occurred during the last 15 years in Italy. A2143G remains the most prevalent point mutation involved, thus suggesting that new therapeutic strategies are needed.

Differential immunohistochemical expression of syndecan-1 and tumor necrosis factor alpha in colonic mucosa of patients with Crohn's disease.

Tumor necrosis factor alpha (TNFalpha) in intestinal mucosa plays a key role in the inflammation characterizing Crohn's disease (CD). Moreover, adhesion molecule syndecan-1 mediates the maintenance of mucosal integrity and supports tissue repair. Therefore, our aim in this study was to correlate simultaneous expression of TNFalpha and syndecan-1 in patients affected by CD. Biopsies from 10 patients with CD of large bowel and 10 subjects with irritable bowel syndrome (controls) were studied by immunohistochemical detection of both TNFalpha and syndecan-1 on successive serial sections. Overall labeling index (OLI) was indicated by the percentage of positive stromal (i.e., nonepithelial) cells/1000 counted in randomized fields, whereas selected labeling index (SLI) was represented by the simultaneous evaluation of both molecules in a same single selected field of each specimen. TNFalpha and syndecan-1 OLI were significantly higher in CD compared with controls, while SLI showed an inverse relationship between the molecules in CD which was not observed in controls. Epithelial syndecan-1 cytoplasmatic staining of superficial epithelium was associated with loss of basolateral staining in the crypts and high stromal TNFalpha in CD. In conclusion, TNFalpha and syndecan-1 expression is increased in the intestinal mucosa of patients with CD. However, the expression of the two molecules is inversely related when a single field is considered, these data supporting the possibility of a downregulation exerted by TNFalpha.

Gastric epithelial cell proliferation and ras oncogene p21 expression in first-degree relatives of gastric cancer patients: a case-control study.

OBJECTIVES: Individuals with a family history of gastric cancer have an increased risk of developing such neoplasia. This study aimed to assess epithelial cell proliferation and ras oncogene mutation in such individuals. METHODS: Twenty dyspeptic, first-degree relatives of patients with gastric cancer and 20 matched controls were enrolled. Endoscopy with biopsies was performed in all cases. Gastric specimens were used to look for Helicobacter pylori infection and to assess both epithelial cell proliferation and ras oncogene expression by immunohistochemistry. RESULTS: Cell proliferation values were not significantly different between the patient and control groups (18.1 +/- 7.1 versus 18.9 +/- 7.4; P = 0.7). Overall, ras mutation was detected in five out of 40 cases, and its distribution was similar between patients and controls (20 versus 10%; P = 0.9), as well as between H. pylori-positive and negative patients (22 versus 9%; P = 0.2). Cell proliferation values tended to be higher in cases with ras mutation than in those without (25.2 +/- 9.4 versus 16.8 +/- 5.8; P = 0.08). Cell proliferation values were significantly higher in H. pylori-positive cases compared with uninfected cases, in both patient (24.7 +/- 4.7 versus 12.5 +/- 2.4; P = 0.0003) and control (25.9 +/- 4.8 versus 13.3 +/- 2.8; P = 0.0003) groups. CONCLUSIONS: Both gastric cell proliferation values and ras mutation prevalence did not differ between first-degree relatives of gastric cancer patients and controls. H. pylori infection similarly increased the proliferation index of gastric mucosa in both groups.

Clarithromycin-resistant genotypes and eradication of Helicobacter pylori.

BACKGROUND: Three point mutations (A2143G, A2142G, and A2142C) have been involved in Helicobacter pylori clarithromycin resistance. OBJECTIVE: To compare the eradication rates among the different point mutations and the efficacy of triple therapy and a sequential regimen according to genotypic resistance. DESIGN: Post hoc subgroup study from a multicenter, randomized trial. SETTING: Two hospitals in central and southern Italy between January and December 2001. PATIENTS: 156 patients with H. pylori infection. MEASUREMENTS: Real-time polymerase chain reaction for assessing clarithromycin resistance; histology, rapid urease test, and 13C-urea breath test at entry and after 4 to 6 weeks. INTERVENTION: 7-day triple therapy (20 mg of rabeprazole, 500 mg of clarithromycin, and 1 g of amoxicillin) in 75 patients or a 10-day sequential regimen (20 mg of rabeprazole plus 1 g of amoxicillin for 5 days and 20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of tinidazole for the remaining 5 days) in 81 patients. All drugs were given twice daily. RESULTS: Helicobacter pylori infection was eradicated in 11 of 23 patients (48%) with the A2143G mutation and in 14 of 15 patients (93%) with either A2142G or A2142C strains (difference, 45 percentage points [95% CI, 15 to 65 percentage points]; P = 0.004). The sequential regimen achieved a higher cure rate than triple therapy in A2143G mutate strains (difference, 49 percentage points [CI, 8 to 72 percentage points]; P = 0.024). LIMITATIONS: The post hoc substudy design may require further confirmation. Other limitations are the accessibility to the tool and the cost of investigations (70 euros per patient). CONCLUSIONS: The A2143G mutation seemed to be associated with a very low eradication rate. The sequential regimen achieved a higher cure rate than standard therapy even in patients with these strains.

Claritromycin resistance and Helicobacter pylori genotypes in Italy.

The relationship between H. pylori clarithromycin resistance and genetic pattern distribution has been differently explained from different geographic areas. Therefore, we aimed to assess the clarithromycin resistance rate, to evaluate the bacterial genetic pattern, and to search for a possible association between clarithromycin resistance and cagA or vacA genes. This prospective study enrolled 62 consecutive H. pylori infected patients. The infection was established by histology and rapid urease test. Clarithromycin resistance, cagA and vacA status, including s/m subtypes, were assessed on paraffin-embedded antral biopsy specimens by TaqMan real time polymerase chain reaction (PCR). Primary clarithromycin resistance was detected in 24.1 % of cases. The prevalence of cagA was 69.3 %, and a single vacA mosaicism was observed in 95.1 % cases. In detail, the s1m1 was observed in 23 (38.9 %) patients, the s1m2 in 22 (37.2 %), and the s2m2 in 14 (23.7 %), whereas the s2m1 combination was never found. The prevalence of cagA and the vacA alleles distribution did not significantly differ between susceptible and resistant strains. Primary clarithromycin resistance is high in our area. The s1m1 and s1m2 are the most frequent vacA mosaicisms. There is no a relationship between clarithromycin resistance and bacterial genotypic pattern and/or cagA positivity.

A new semiquantitative method of quantifying Helicobacter pylori in antigen stools.

Stool antigen test for Helicobacter pylori, a noninvasive assay, is emerging as a strong competitor to urea breath test (UBT). Nevertheless, although the UBT delta value is a semiquantitative indicator of H. pylori intragastric load, until now the H. pylori stool antigen test has been used only as a qualitative investigation. We report here the results of a study performed with the aim of obtaining a semiquantitative measurement of bacterial amount in stools. We studied 15 patients with dyspepsia using H. pylori positivity at histology, the rapid urease test, UBT, and the H. pylori stool antigen test. The result of this last test was expressed by a numerical value we obtained by applying the principle of "standard points" to the absorbance units at spectrophotometric reading. This measurement was previously validated by testing probe sampling of H. pylori stool antigen with known pure and stool-mixed bacterial amounts. A numerical result for H. pylori stool antigen was correlated to UBT delta for each patient using Pearson's r test. Finally, a Student t test was performed to investigate possible differences in UBT and H. pylori stool antigen test values between anti-CagA-positive and -negative patients. We obtained a curve of saturation with both known amount of pure and stool-mixed bacteria. Pearson's r test showed a significant correlation between UBT delta value and H. pylori stool antigen measurement (r = 0.77; p < 0.001). Urea breath test delta and H. pylori stool antigen test values were significantly higher in anti-CagA-positive patients. Our data suggest that a numerical estimation of H. pylori stool antigen may be feasible. This evaluation, similarly to UBT delta, may represent a semiquantitative determination of bacterial intragastric load.