Scientific Evidence

Background and Aim: Hemorrhoidal Disease (HD) is a chronic pathology and is fairly common in the general population. For this reason, conservative therapies need to be at the same time effective and tolerated. The topical medications available usually contain either a combination of local anesthetics with anti-inflammatories or muscle relaxants, thus addressing a single mechanism, if any, of those that underlie symptoms onset. As a consequence, evidence of efficacy of these drugs is currently limited and the needed tolerability and safety from a topical treatment of HD is not always evident. The aim of the present study was to evaluate efficacy and tolerability of a 100% natural ointment, a medical device made of substances, for the symptomatic treatment of HD. Methods: Symptomatic grade I or II HD patients with 0-100 VAS score for HD-related
discomfort ≥ 30 were treated for 10 days. Outcome measures included variation of HD subjective symptoms (discomfort, pain, itching and burning) and objective signs (bleeding and anal leakage) at day 3, 7 and 10, and the presence of prolapse after treatment. Statistical analysis: for the analysis of the primary endpoint (i.e. reduction of discomfort), missing data in the full analysis set (FAS) population were replaced using the “Last Observation Carried Forward” (LOCF) method. For the analyses of secondary endpoints, Poisson mixed model was used to evaluate symptom variation (VAS). Bleeding and anal leakage were recoded as negative or positive in two different variables (grade 1 and 2) derived from their frequency (i.e., for grade1, each of the clinical signs was considered Negative if the patient reported frequency was “Never”; recoded as Positive if any other frequency category was reported) and frequencies of positive patients in each grade were compared by Logistic Mixed model. Mixed models were used to take in account repeated data for the same subject. Missing values in quantitative data analysing by Mixed model were imputed by statistical interpolation. In analysing bleeding, anal leakage and presence of prolapse in FAS population, missing data where either replaced using the LOCF method or imputed as positive (i.e., worst case).
Results: 45 patients were enrolled. Data showed a significant reduction of discomfort in treated patients both during and after treatment (p<0.001 at all-time points evaluated), with a median VAS score decrease of 30 points after treatment when compared to baseline. The same significant reduction (p<0.001) was shown for all other symptoms either at the end of treatment or at earlier time points, both in PP and FAS populations. As for objective signs, a significant reduction was observed, at each time point compared to baseline, in the number of patients from the PP population positive for bleeding (p<0.001) and anal leakage (p<0.05). A similar evolution was shown in FAS population, where reduction was progressive over the 10-day treatment and statistically significant or almost significant irrespectively of imputation method used. In 6 out of 10 patients presenting prolapse at baseline, prolapse was no more evident after treatment. No treatment-related adverse events were registered.
Conclusion: The class IIb medical device made of substances under study is a valid, highly tolerated and safe therapeutic option in medical management of grade I and II HD. Trial
registration NCT03545724 2018.06.04.

Background: Polyethylene glycol (PEG) is recommended as first-line treatment of pediatric functional constipation. However, the oral route of administration is often poorly feasible in children mostly due to poor palatability. Promelaxin microenemas exert a topical evacuative action and may offer a valuable option in pediatric FC.
Aim: To assess whether Promelaxin microenemas would be non-inferior to PEG 4000 in young children with FC.
Methods: This is a randomized, open-label, multi-centric, non-inferiority trial enrolling infants and young children aged 6–48 months, with FC according to Rome III criteria. After 1 week of run in, children were randomized to 2 weeks of Promelaxin or PEG, followed by a 6-week on-demand treatment period. Primary endpoint was response rate to randomized treatment, with “response” defined as at least 3 evacuations per week and an average increase of at least one evacuation per week as compared to baseline. Safety, stool consistency and the analysis of fecal microbiota were secondary endpoints.
Results: Out of the 158 patients who entered the trial, 153 patients were treated (77 and 76, PEG and Promelaxin arm, respectively). In the primary analysis, the 95% confidence interval (CI) for the treatment's effect lay entirely above the non-inferiority margin in both Full Set (FAS) and Per Protocol (PP) analyses, providing evidence of the non-inferiority of Promelaxin vs. PEG 4000 [response rate difference: 16.5% (CI 1.55–31.49%) and 11.03% (CI −5.58 to 27.64%), FAS and PP analyses, respectively]. Mean compliance to the randomized treatment was >80% in both arms. Secondary endpoints did not significantly differ between the two arms, except for the average number of total days of on-demand treatment that was significantly lower in the Promelaxin arm [14.6 (12.7) vs. 9.8 (9.1), mean (SD); primary endpoint responders in PEG and Promelaxin arm, respectively; p = 0.027]. Microbiota evenness significantly increased in the PEG 4000 arm at V4 as compared to the Promelaxin arm (p < 0.05). In addition, at V5, patients treated with PEG showed a significantly decreased microbiota density as compared to patients treated with Promelaxin (p = 0.036).
Conclusions: Promelaxin microenemas are non-inferior to oral PEG in children with FC.

Abdominal pain is a frequent symptom of irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBDs). Although the knowledge of these pathologies is progressing, new therapeutic strategies continue to be investigated. In the present study, the effect of a system of molecules of natural origin (a medical device according to EU Directive 93/42/EC, engineered starting from Boswellia serrata resins, Aloe vera polysaccharides and Matricaria chamomilla and Melissa officinalis polyphenols) was evaluated against the intestinal damage and visceral pain development in DNBS-induced colitis model in rats. The system (250 and 500 mg kg−1) was orally administered once daily, starting three days before the injection of 2,4-dinitrobenzenesulfonic acid (DNBS) and for 14 days thereafter. The viscero-motor response (VMR) to colon-rectal balloon distension (CRD) was used as measure of visceral sensitivity. The product significantly reduced the VMR of DNBS-treated animals. Its effect on pain threshold was better than dexamethasone and mesalazine, and not lower than amitriptyline and otilonium bromide. At microscopic and macroscopic level, the tested system was more effective in protecting the intestinal mucosa than dexamethasone and mesalazine, promoting the healing of tissue lesions. Therefore, we suggest that the described system of molecules of natural origin may represent a therapeutic option to manage painful bowel diseases.

Background: AG is the most common cause of pediatric consultations among children between 2 and 5 years of age and it still leads to high mortality and morbidity. Its management is based on rehydration therapy, but this treatment is not effective in reducing duration of diarrhea. For this reason, other safer and less expensive interventions, which could be added to oral rehydration therapy, are of great interest.
Methods: A pilot, randomized, case-controlled trial was conducted in 60 children affected by AG (< 7 days) with mild-moderate dehydration, according to WHO recommendations, from1 year to 17 years old. Patients were divided into 2 Groups: Group 1 consisting of 30 children treated with Actitan F and standard oral rehydration (SOR); Group 2 consisting of 30 children who received only SOR. Both groups received treatment for seven days, respectively. Patients of Group 1 stopped for their own choice, SOR after the first 24 h and continued only with Actitan F.
Results: After 24 h of treatment, the median number of stools was 3.5 for Group 1, and 4 for Group 2. In Group 1 the difference between the number of stools at baseline (n = 5) and after 24 h of treatment (n = 3.5) was significant (p < 0.0001). At the end of treatment, the median duration of diarrhea in Group 1 was 5 days, compared with 4 days in the Group 2, this difference was not statically significant (p 0.48).
Conclusions: Oral administration of Actitan F associated with SOR seems safe and effective treatment in shortening the duration of AG in children. Further studies confirming these data are needed.

OBJECTIVES: The integrity of the esophageal mucosal barrier is the first mechanism of protection against gastro-esophageal reflux. A possible strengthening action of esophageal mucosal barrier could be given by topical agents that act by reducing its permeability. Our aim was to test the protective effect of a medical device made of substances (MDMS), composed by natural complex (polysaccharides and flavonoids) and minerals (limestone and nahcolite), by assessing the functional integrity of the esophageal mucosa, before and after exposure to an acidic solution. The experiment was done in control subjects and the effect was compared to what observed with a sodium alginate solution (SA). METHODS: Three distal esophageal biopsies were obtained from 14 patients without symptoms of GERD or alterations of esophageal mucosa. The biopsies were mounted in mini-Ussing chambers and Trans Epithelial Electrical Resistance (TER, Ohm/cm2 ) was evaluated in basal conditions after exposure to neutral solutions (Krebs-Henseleit at pH 7.4 and 37°C) and after exposure to acidic solutions (Krebs - Henseleit at pH 2+1 mg/ml porcine pepsin Sigma-Aldrich + 1 mM taurodeoxycholic acid Sigma-Aldrich). For each patient one biopsy was used as control, while the other two biopsies were pre-treated for 5 minutes with topical products, before exposure to acidic solution. Each step of the experiment (neutral solution, topical treatment, acidic solution, neutral solution) lasted 30 minutes. RESULTS: Biopsies of 12 patients were analyzed (two were considered inadequate) and mean value of TER of the last 5 minutes of each 30 min-step was calculated. In control biopsies, acidic solution exposure induced a significant reduction of TER (108.7 ± 59.2 to 88.1 ± 48.1, p