Endoscopic Submucosal Dissection of Gastric Neoplastic Lesions. An Italian, Multicenter Study

Endoscopic submucosal dissection (ESD) allows removing neoplastic lesions on gastric mucosa, including early gastric cancer (EGC) and dysplasia. Data on ESD from Western countries are still scanty. We report results of ESD procedures performed in Italy. Data of consecutive patients who underwent ESD for gastric neoplastic removal were analyzed. The en bloc resection rate and the R0 resection rates for all neoplastic lesions were calculated, as well as the curative rate (i.e., no need for surgical treatment) for EGC. The incidence of complications, the one‐month mortality, and the recurrence rate at one‐year follow‐up were computed. A total of 296 patients with 299 gastric lesions (80 EGC) were treated. The en bloc resection was successful for 292 (97.6%) and the R0 was achieved in 266 (89%) out of all lesions. In the EGC group, the ESD was eventually curative in 72.5% (58/80) following procedure. A complication occurred in 30 (10.1%) patients. Endoscopic treatment was successful in all 3 perforations, whereas it failed in 2 out of 27 bleeding patients who were treated with radiological embolization (1 case) or surgery (1 case). No procedure‐related deaths at one‐month follow‐up were observed. Lesion recurrence occurred in 16 (6.2%) patients (6 EGC and 10 dysplasia). In conclusion, the rate of both en bloc and R0 gastric lesions removal was very high in Italy. However, the curative rate for EGC needs to be improved. Complications were acceptably low and amenable at endoscopy

Provoked Vestibulodynia and Topical Treatment: A New Option

Background: Provoked vestibulodynia is commonly associated with dyspareunia and affects 7% to 15% of women. This pathology has major implications on sexual function and quality of life, and several types of treatments are available for its management. However, a consensus has not been reached concerning the best treatment of vulvar pain. The aim of this study was to assess the efficacy and safety of a brand-new product, the vulvar emulgel Meclon (R) Lenex, for the management of provoked vestibulodynia and non-infective vulvitis. Methods: This was a monocentric, prospective, randomized, double-blind and placebo-controlled study. We enrolled 40 women with provoked vestibulodynia; 20 patients received Meclon (R) Lenex, whereas the remaining received a placebo. Each woman was assessed subjectively (through questionnaires) and objectively by evaluating vaginal and vulvar symptoms (Friedrichs criteria and Marinoff dyspareunia grade). We evaluated efficacy, safety, compliance and tolerability of the brand-new product vulvar gel Meclon (R) Lenex in provoked vestibulodynia. Results: After administration of Meclon (R) Lenex, we evaluated all parameters of the Friedrichs criteria (burning, dyspareunia, erythema, vulvar pain at the 5 o'clock position and 7 o'clock position), as well as the levels of Marinoff dyspareunia. The active treatment showed to be statistically significantly effective (p value <= 0.05) in reducing all symptoms of Friedrichs criteria, vulvar pain and Marinoff dyspareunia. Conclusion: This prospective study showed that Meclon (R) Lenex vulvar emulgel revealed an excellent tolerability and compliance, demonstrating to be a safe and effective option in the treatment of provoked vestibulodynia and non-infective vulvitis

A Randomized Controlled Trial Comparing a New D-Mannose-based Dietary Supplement to Placebo for the Treatment of Uncomplicated Escherichia coli Urinary Tract Infections

Background: The rise in antimicrobial resistance means that alternative approaches for the treatment and prevention of urinary tract infection (UTIs) are required. Objective: To evaluate the safety and efficacy of a D-mannose-based dietary supplement (D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion; DAPAD complex) for the treatment of uncomplicated acute E. coli UTIs. Design, setting, and participants: This was a single-center, randomized, double-blind, placebo-controlled trial conducted from April 2021 to October 2021 in Rajalakshmi Hospital and Research Centre (Bangalore, India). The participants were nonmenopausal women with an acute uncomplicated E. coli UTI. UTI was diagnosed according to the presence of at least one urinary symptom and bacteriuria (>100 000 CFU/ml). Intervention: The DAPAD complex was administered twice a day for 5 d, with phenazopyridine and alkalizing agents as the standard of care (SOC). The control group received placebo with SOC. Outcome measurements and statistical analysis: Subjective (clinical resolution/response) and objective (midstream bacteriuria) outcomes were evaluated at the end of therapy (day 6) and at day 35 of follow-up. Adverse events were recorded. Categorical variables were analyzed using χ2 and Fisher's exact tests; a p value <0.05 was considered significant. Results and limitations: Seventy women were enrolled and equally randomized to the two groups. Clinical resolution was higher in the DAPAD group at 6 d (34.3% vs 0%; p < 0.0001) and 35 d from baseline (88.6% vs 20%, p < 0.0001). At day 35, no patients in the DAPAD group had moderate or severe symptoms, whereas 25.7% (nine/35) and 11.4% (four/35) of patients in the placebo group had moderate and severe symptoms, respectively. Bacteriological resolution was also higher in the DAPAD group at day 6 (85.7% vs 14.3%; p < 0.0001) and day 35 (100% vs 40%; p < 0.0001). Three mild adverse events (4.26%) unrelated to the investigated product were recorded, all of which were medically treated. Conclusions: The DAPAD complex dietary supplement is effective and safe for treatment of acute uncomplicated E. coli UTIs. Patient summary: Our results show that for nonmenopausal women with an uncomplicated Escherichia coli urinary tract infection, those treated with a dietary supplement (containing D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion) had a higher rate of clinical resolution or response than women who received a placebo

T-wave axis deviation, metabolic syndrome and estimated cardiovascular risk in men and women of the MOLI-SANI Study

Aim: We aimed at investigating the association between T-wave axis deviation, metabolic syndrome (MetS), its components and estimated risk of cardiovascular disease (CVD) at 10 years in a adult Italian population. Methods: 11,143 women (54±11 years) and 9,742 men (55±11 years) were analysed from the Molisani cohort, randomly recruited from the general population. MetS was defined using the ATPIII criteria. T-wave axis deviation was measured from the standard 12-lead resting electrocardiogram. CVD risk in ten years was estimated by the CUORE score. Results: 29% of men and 27% of women with MetS showed borderline or abnormal T-wave as compared to 24% and 17% without MetS (p<0.0001 for both genders). Among components of MetS, elevated waist and blood pressure were strongly associated with Twave axis deviation, whereas glucose, HDL and triglycerides were only marginally. The odds of having borderline or abnormal T-wave axis deviation in multivariable regression analysis, was 1.38 (95% CI:1.25-1.53) in MetS men and 1.68 (95% CI:1.51-1.87) in MetS women compared to those without. Further adjustment for MetS components completely abolished the associations. Abnormal T-wave axis deviation was associated with an increased risk of CVD in 10 years in men (OR=4.4; 95% CI:1.10-17.9). Conclusion: T-wave axis deviation is strongly associated with components of the MetS, in particular high waist circumference and blood pressure and with an increased CVD risk, particularly in men. ECG monitoring to identify T-wave axis deviation in obese, hypertensive or MetS subjects can be an early indicator of vascular disease and help in reducing cardiac events

SPECIFIC DYSPEPTIC SYMPTOMS ARE ASSOCIATED WITH POOR RESPONSE TO THERAPY IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE

Background: In gastroesophageal reflux disease (GORD) patients, coexistence of functional dyspepsia (FD) is known to be associated with poor response to proton pump inhibitors (PPIs), but the contribution of specific dyspepsia symptoms has not been systematically investigated yet. Objective: To characterize the impact of dyspepsia symptoms on PPIs response in GORD patients. Methods:. The enrolled subjects were 100 patients with diagnosis of GORD. All patients underwent a 24 hour pH-impedance test, while on PPIs-therapy. Patients were divided into two groups, refractory and responders, according to the persistence of GORD symptoms. A standardized questionnaire for FD was also administered to assess presence of dyspepsia symptoms. Results: In the subgroup of refractory patients FD was more prevalent than in responder ones, with postprandial fullness, nausea, vomiting, early satiation and epigastric pain being significantly prevalent in refractory GORD-patients. In the multivariate analysis only early satiation and vomiting were significantly associated with poor response to PPIs Conclusion: Coexistence of FD is associated with refractory-GORD. We showed that only early satiation and vomiting are risk factors for poor response to PPIs therapy. Our findings suggest that symptoms of early satiation and vomiting would help to identify the subset of PPIs-refractory GORD patients

Endoscopic submucosal dissection of gastric neoplastic lesions: An Italian, multicenter study

Endoscopic submucosal dissection (ESD) allows removing neoplastic lesions on gastric mucosa, including early gastric cancer (EGC) and dysplasia. Data on ESD from Western countries are still scanty. We report results of ESD procedures performed in Italy. Data of consecutive patients who underwent ESD for gastric neoplastic removal were analyzed. The en bloc resection rate and the R0 resection rates for all neoplastic lesions were calculated, as well as the curative rate (i.e., no need for surgical treatment) for EGC. The incidence of complications, the one-month mortality, and the recurrence rate at one-year follow-up were computed. A total of 296 patients with 299 gastric lesions (80 EGC) were treated. The en bloc resection was successful for 292 (97.6%) and the R0 was achieved in 266 (89%) out of all lesions. In the EGC group, the ESD was eventually curative in 72.5% (58/80) following procedure. A complication occurred in 30 (10.1%) patients. Endoscopic treatment was successful in all 3 perforations, whereas it failed in 2 out of 27 bleeding patients who were treated with radiological embolization (1 case) or surgery (1 case). No procedure-related deaths at one-month follow-up were observed. Lesion recurrence occurred in 16 (6.2%) patients (6 EGC and 10 dysplasia). In conclusion, the rate of both en bloc and R0 gastric lesions removal was very high in Italy. However, the curative rate for EGC needs to be improved. Complications were acceptably low and amenable at endoscopy

Discovering anomalies in big data: a review focused on the application of metaheuristics and machine learning techniques

With the increase in available data from computer systems and their security threats, interest in anomaly detection has increased as well in recent years. The need to diagnose faults and cyberattacks has also focused scientific research on the automated classification of outliers in big data, as manual labeling is difficult in practice due to their huge volumes. The results obtained from data analysis can be used to generate alarms that anticipate anomalies and thus prevent system failures and attacks. Therefore, anomaly detection has the purpose of reducing maintenance costs as well as making decisions based on reports. During the last decade, the approaches proposed in the literature to classify unknown anomalies in log analysis, process analysis, and time series have been mainly based on machine learning and deep learning techniques. In this study, we provide an overview of current state-of-the-art methodologies, highlighting their advantages and disadvantages and the new challenges. In particular, we will see that there is no absolute best method, i.e., for any given dataset a different method may achieve the best result. Finally, we describe how the use of metaheuristics within machine learning algorithms makes it possible to have more robust and efficient tools

Cardiovascular risk profile and lifestyle habits in a cohort of Italian cardiologists. Results of the SOCRATES survey

Objectives. To offer a snapshot of the personal health habits of Italian cardiologists, the Survey on Cardiac Risk Profile and Lifestyle Habits in a Cohort of Italian Cardiologists (SOCRATES) study was undertaken. Background. Cardiologists' cardiovascular profile and lifestyle habits are poorly known worldwide. Methods. A Web-based electronic self-reported survey, accessible through a dedicated website, was used for data entry, and data were transferred via the web to a central database. The survey was divided in 4 sections: baseline characteristics, medical illnesses and traditional cardiovascular risk factors, lifestyle habits and selected medication use. The e-mail databases of three national scientific societies were used to survey a large and representative sample of Italian cardiologists. Results. During the 3-month period of the survey, 1770 out of the 5240 cardiologists contacted (33.7%) completed and returned one or more sections of the questionnaire. More than 49% of the participants had 1 out of 5 classical risk factors (e.g. hypertension, hypercholesterolemia, active smoking, diabetes and previous vascular events). More than 28% of respondents had 2 to 5 risk factors and only 22.1% had none and therefore, according to age and sex, could be considered at low-intermediate risk. Despite the reported risk factors, more than 90% of cardiologists had a self-reported risk perception quantified as mild, such as low or intermediate. Furthermore, overweight/obesity, physical inactivity and stress at work or at home were commonly reported, as well as a limited use of cardiovascular drugs, such as statins or aspirin. Conclusions. The average cardiovascular profile of Italian cardiologist is unlikely to be considered ideal or even favorable according to recent statements and guidelines regarding cardiovascular risk. Thus, there is a large room for improvement and a need for education and intervention

From the Amelioration of a NADP+-dependent Formate Dehydrogenase to the Discovery of a New Enzyme: Round Trip from Theory to Practice

NADP+-dependent formate dehydrogenases (FDHs) are biotechnologically relevant enzymes for cofactors regeneration in industrial processes employing redox biocatalysts. Their effective applicability is however hampered by the low cofactor and substrate affinities of the few enzymes described so far. After different efforts to ameliorate the previously studied GraFDH from the acidobacterium Granulicella mallensis MP5ACTX8, an enzyme having double (NAD+ and NADP+) cofactor specificity, we started over our search with the advantage of hindsight. We identified and characterized GraFDH2, a novel highly active FDH, which proved to be a good NAD+-dependent catalyst. A rational engineering approach permitted to switch its cofactor specificity, producing an enzyme variant that displays a 10-fold activity improvement over the wild-type enzyme with NADP+. Such variant resulted to be one of the best performing enzyme among the NADP+-dependent FDHs reported so far in terms of catalytic performance

Endoscopic Submucosal Dissection for Subepithelial Tumor Treatment in the Upper Digestive Tract: A Western, Multicenter Study

Background/aims: Endoscopic submucosal dissection (ESD) has been proposed for removal of gastrointestinal subepithelial tumors (GI-SETs), but data are still scanty. This study aimed to report a case series from a western country. Patients and methods: Data of patients with upper GI-SETs suitable for ESD removal observed in 4 centers were retrospectively reviewed. Before endoscopic procedure, the lesion was characterized by endosonographic evaluation, histology, and CT scan. The en bloc resection and the R0 resection rates were calculated, as well as incidence of complications, and the 1-year follow-up was reported. Results: Data of 84 patients with esophageal (N = 13), gastric (N = 61), and duodenal (N = 10) GI-SETs were collected. The mean diameter of lesions was 26 mm (range: 12-110 mm). There were 17 gastrointestinal stromal tumors, 12 neuroendocrine tumors, 35 leiomyomas, 18 lipomas, and 2 hamartomas. En bloc and R0 resection were achieved in 83 (98.8%) and in 80 (95.2%) patients, respectively. Overall, a complication occurred in 11 (13.1%) patients, including bleeding (N = 7) and perforation (N = 4). Endoscopic approach was successful in all bleedings, but 1 patient who required radiological embolization, and in 2 perforations, while surgery was performed in the other patients. Overall, a surgical approach was eventually needed in 5 (5.9%), including 3 in whom R0 resection failed and 2 with perforation. Conclusions: Our study found that ESD may be an effective and safe alternative to surgical intervention for both benign and localized malignant GI-SETs