Use of Streptococcus salivarius K12 to reduce the incidence of pharyngo-tonsillitis and acute otitis media in children: a retrospective analysis in not-recurrent pediatric subjects.

BACKGROUND: Previous trials, performed in subjects affected by recurrent streptococcal pharyngo-tonsillar infection, have shown that the use for 90 days of Streptococcus salivarius K12 (K12), an oral colonizing probiotic producing lantibiotic bacteriocins, reduces the occurrence of streptococcal and viral pharyngitis and acute otitis media (AOM). The aim was to evaluate the role of K12 in reducing the incidence of streptococcal and viral pharyngo-tonsillitis and AOM when administered in two separate trimesters, from October to December and then from April to June, in pediatric subjects with non-recurrent streptococcal infection. METHODS: We retrospectively analyzed the incidence of pharyngo-tonsillitis and AOM in 133 children by comparing the number of episodes occurring between September 1st, 2014 and August 31st, 2015, when no treatment with K12 was given, with the period between September 1st, 2015 and August 31st, 2016, when K12 was administered. RESULTS: Analysis of the findings for the 133 children demonstrated that K12 use decreased the incidence of pharyngo-tonsillitis by about 90% (P<0.001) and the occurrence of AOM by about 70% (P<0.001) and confirms the high safety profile of the strain. CONCLUSIONS: As already demonstrated in subjects with recurrent streptococcal pharyngo-tonsillar infection, K12, if administered for two trimesters out of 12 months, is associated with a reduced incidence of pharyngitis and AOM in pediatric subjects with non-recurrent streptococcal infection.

Use of a probiotic mixture containing Bifidobacterium animalis subsp. lactis BB12 and Enterococcus faecium L3 in atopic children.

BACKGROUND: Imbalance of the human gut microbiota in childhood, mainly due to low gut biodiversity and a low bifidobacterial load, has been suggested as a risk factor for atopy. Administration of Enterococcus faecium L3 in infants has been shown to increase the gut bifidobacterial count. The aim was to verify if a mixture of Bifidobacterium animalis subsp. lactis BB12 and E. faecium L3 could reduce the signs, symptoms and need for drugs in atopic children. METHODS: We retrospectively analyzed, and compared with controls, clinical outcomes following use of BB12 and L3 strains when administered 3 months before or during the development of signs and symptoms of atopy. RESULTS: When administered in the 3 months before the development of atopy, the BB12 and L3 strains significantly reduced (P<0.001) rhinitis, watery eyes and cough/bronchospasm. However, reduced efficacy was observed when the mixture was given during the 3 months of atopy. The mixture of strains also significantly reduced the use of oral antihistamines, inhaled corticosteroids (in the same children in two different years) and oral corticosteroids (in different children in the same year). CONCLUSIONS: When administered as a prophylactic, the mixture of BB12 and L3 (iNatal Ped®) statistically decreases the signs and symptoms of atopy and reduces the use of drugs. Administration of the same probiotics as treatment after the appearance of atopy is less effective.

Effects of Greenselect Phytosome® on weight maintenance after weight loss in obese women: a randomized placebo-controlled study.

BACKGROUND: Most subjects regain weight after weight loss due to compensatory adaptations finalized to maintain stable body energy stores. Green tea (GT) preparations, which help maintain energy expenditure while dieting could be a useful strategy to facilitate weight maintenance. The usefulness of GT preparations in weight maintenance has been poorly studied so far with conflicting results. This study evaluated if a supplement of GSP and piperine helps obese women to maintain the weight loss obtained with a 3-month lifestyle intervention. METHODS: In a randomized placebo-controlled study, we examined whether a highly bioavailable GT extract may counteract weight regain after weight loss. Forty obese women (age 50.1 ± 10.1 years, Body Mass Index (BMI) 36.3 ± 2.7 kg/m(2)) underwent a 3-month lifestyle intervention. At the end of the intervention, the women were randomized in two groups for the weight-maintenance phase: 20 of them were prescribed twice a day, for 3 months, with a formula containing 150 mg/dose of Greenselect Phytosome® and 15 mg/dose of pure piperine (GSP group), and 20 were given placebo (P group). Anthropometric measures and body composition were measured before (V-3) and after lifestyle intervention (V0), 1 (V1), 2 (V2), and 3 (V3) months after prescribing supplements and 3 months following the discontinuation of supplements (V6). RESULTS: Lifestyle intervention induced a significant weight reduction in both groups with similar weight change (-6.2 ± 2.6 in GSP group vs. -4.8 ± 3.1 % in P group). In the GSP group, V1 in comparison to V0, had further reduction in weight and fat mass, which remained stable at V2 and V3 and increased at V6. In the P group, weight and fat mass increased from V2 onwards. Weight changes in GSP group and P group from V0 to V3 were -1.0 kg (95 % CI -2.5 to +0.5) and + 0.3 kg (95 % CI -0.9 to +1.6), respectively. The proportion of women with weight loss ≥ 5 % was greater in the GSP group than in the P group (75 % vs. 45 % at V1, and 60 % vs. 30 % at V6, p < 0.05 for both groups). CONCLUSIONS: Greenselect Phytosome® devoid of caffeine may have a clinical potential for the maintenance of weight after intentional weight loss. TRIAL REGISTRATION: Clinicaltrials.gov NCT02542449 (September 2015).

Is Implantation of a Left Ventricular Assist Device in Patients With Critical or Impending Cardiogenic Shock an Absolute Contraindication? Looking Back at Our Past Experience Trying to Identify Contraindicative Risk Factors.

Poor survival has been demonstrated after ventricular assist device (VAD) implantation for Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 and 2 patients compared with more stable levels. However, risk factors within this high-risk cohort have not been determined so far. The aim of the present study was to identify risk factors associated with this very high mortality rate. Between February 1993 and January 2013, 298 patients underwent VAD implantation in our institution. One hundred nine patients were in INTERMACS level 1 and 49 patients were in INTERMACS level 2 and were therefore defined as hemodynamically critical (overall 158 patients). Assist devices implanted were: HVAD HeartWare n = 18; Incor n = 11; VentrAssist n = 2; DeBakey n = 22; and pulsatile systems n = 105. After cumulative support duration of 815.35 months, Kaplan-Meier analysis revealed a survival of 63.9, 48.8, and 40.3% at 1, 6, and 12 months, respectively. Cox regression analyses identified age > 50 (P = 0.001, odds ratio [OR] 2.48), white blood cell count > 13.000/µL (P = 0.01, OR 2.06), preoperative renal replacement therapy (P = 0.001, OR 2.63), and postcardiotomy failure (P < 0.001, OR 2.79) as independent predictors of mortality. Of note, last generation VADs were not associated with significantly better 6-month survival (P = 0.59). Patients without the aforementioned risk factors could yield a survival of 79.2% at 6 months. This single-center experience shows that VAD implantation in hemodynamically unstable patients generally results in poor early outcome, even in third-generation pumps. However, avoiding the aforementioned risk factors could result in improved outcome.

Role of a medical device for intra-vaginal use in improving the quality of the colposcopic examination and the anatomical/pathological reading of the cytological test and biopsy.

To evaluate the efficacy of a vaginal suppository in overcoming unsatisfactory colposcopy and/or possible change in terms of diagnosis in women who have had abnormal cervical cytology, 98 females were enrolled and treated for 10 days with Kramegin®, a vaginal product in tablets containing Lactobacillus acidophilus, lactic acid and Krameria triandra extract. Seventy-eight of 98 females completed the study. Seventy-fife of 78 volunteers served for the statistical analysis. According to the results got, diagnoses were modified in almost 62% of cases; cervical conization was reduced in 58% of cases; regression for HSIL (to LSIL) was 35% higher than expected; need of follow-up decreased by 36% and treatment was well tolerated in about 96% of cases. Use of Kramegin® before colposcopy can be considered a good tool to increase the possibility of turning unsatisfactory colposcopy into satisfactory and seems to indicate a possible role in reducing cervical lesion progression. Deeper clinical investigations are mandatory to confirm this possible result.

Geographical differences in the prevalence of chronic polypharmacy in older people: eleven years of the EPIFARM-Elderly Project.

PURPOSE: To compare the geographical differences in the prevalence of chronic polypharmacy in community-dwelling older people over 11 years. METHODS: This study analyzed nearly two million patients aged 65-94 years recorded in the Drug Administrative Database of the Lombardy Region (Northern Italy) from 2000 to 2010. Chronic polypharmacy was defined as taking five or more drugs in 1 month for at least 6 months (consecutive or not) in a year. RESULTS: There was a significant spatial autocorrelation that increased at the municipality level from 2000 (Moran's I Index = 0.26, z score = 16.91, p < 0.0001) to 2010 (Moran's I Index = 0.36, z score = 23.78, p < 0.0001). Clusters of high (Z(G) > 1.96) and low (Z(G) < -1.96) prevalence rates of chronic polypharmacy were found and were not influenced by age. Chronic polypharmacy weakly correlated with hospital admission (2000: ρ = 0.08, p = 0.0032; 2005: ρ = 0.11, p < 0.0001; 2010: ρ = 0.18, p < 0.0001), but not with mortality. CONCLUSIONS: There were geographical differences in the prevalence of older people with chronic polypharmacy that were only partly explained by health indicators. Targeted activities on prescription practice to ensure that the prescribing of chronic polypharmacy is appropriate are required.

Therapeutic drug monitoring in Crohn's disease patients treated with anti-TNF: a comparison of two techniques.

BACKGROUND: Therapeutic drug monitoring is a useful clinical decision aid in managing patients with inflammatory bowel disease treated with anti-tumor necrosis factor (anti-TNF). Various techniques are available to evaluate drug trough levels, and among these a point-of-care (POC) method has been proposed to overcome the limitations inherent to other methodologies. In this study we aimed to evaluate the capability of POC to discriminate between relapse and remission disease phases, and to assess the concordance of the POC and homogeneous mobility shift assay (HMSA) results. METHODS: Drug trough level of 46 Crohn's disease patients treated with either adalimumab or infliximab were evaluated with both a POC technique and an HMSA at various time points (week-16 and -48) during anti-TNF treatment. RESULTS: Median adalimumab trough level of patients in remission were significantly higher as compared to relapsing patients using both HMSA (week 16, P = 0.0001; week48, P = 0.001) and POC (week 16, P = 0.0003; week 48, P = 0.0012), and similar results were observed with infliximab trough level at week 16 (HMSA, P = 0.019; POC, P = 0.0072). Overall, we observed a good correlation between the techniques for both infliximab (r = 0.76; P < 0.0001) and adalimumab (r = 0.75; P < 0.0001), with no difference in discriminatory accuracy between assays (infliximab: HMSA versus POC c-index, 0.921 versus 0.895, P =0.149; adalimumab: HMSA versus POC c-index, 0.817 versus 0.850, P = 0.197). CONCLUSION: Both POC and HMSA assays are able to reliably differentiate relapse and remission phases in Crohn's disease patients treated with anti-TNF. These techniques showed good concordance and we feel that their preferential use should be based on local accessibility, physicians' experience and preference, and the need for timeliness availability of results.

Use of a probiotic mixture containing Bifidobacterium animalis subsp. lactis BB-12 and Enterococcus faecium L3 as prophylaxis to reduce the incidence of acute gastroenteritis and upper respiratory tract infections in children.

BACKGROUND: For healthy children, attending communities such as nurseries, kindergartens or schools, exposes them to the risk of acute gastroenteritis (AGE) and/or upper respiratory tract infections (URTIs). We therefore evaluated whether the use of a well-documented probiotic formula could act as prophylaxis for AGE and URTIs, reducing the risk of occurrence. METHODS: In a randomized study, we tested a probiotic mixture containing Bifidobacterium animalis subspecies lactis BB-12 and Enterococcus faecium L3 on 94 healthy children, comparing the incidence and duration of episodes of AGE and the incidence of URTIs to those of a control group of 109 healthy, untreated subjects. In a subgroup consisting of 34 healthy, treated children, we also evaluated salivary IgA levels. RESULTS: The use of the probiotic formula significantly reduced the incidence and duration of episodes of AGE by 82% and 45%, respectively, and the incidence and duration of episodes of URTIs by 84% and 50%. Salivary IgA levels significantly increased three-fold after 90 days of probiotic treatment. The probiotic formula was well tolerated and no side effects occurred. CONCLUSIONS: According to our results, use of the probiotic strains BB-12 and L3 statistically reduced the risk of AGE and URTIs in healthy children and increased levels of salivary IgA.

Role in depression of a multi-fractionated versus a conventional Hypericum perforatum extract.

BACKGROUND: Hypericum perforatum is used as medicinal plant for mild to moderately severe depression. Several trials have found hypericum to be more effective than placebo or some antidepressant drugs, but the exact mechanism and most relevant compounds are still unclear. A possible hypothesis is that the antidepressant activity might be due to its multiplicity of bioactive compounds. Aim is to test if greater chemical complexity could result in a greater hypericum antidepressant action. METHODS: A retrospective, 12-month, open-label, observational, controlled trial was conducted to compare the antidepressant clinical activity of a conventional Hypericum perforatum (C-Hp) versus a multi-fractionated (M-Hp) one (IperiPlex®). RESULTS: Treatment with C-Hp demonstrated no efficacy after 6 months and partial (P<0.05) efficacy after 12 months. Treatment with MF-Hp demonstrated highly (P<0.01) significant results at both 6 and 12 months. Analysis of the monthly reduction coefficient demonstrated that treatment with MF-Hp was twice as effective as treatment with C-Hp (0.96 versus 0.48). No side effects were reported. CONCLUSIONS: A multi-fractionated hypericum extract has better clinical outcomes in subjects with depression without determining an increased risk of toxicity or reduced tolerability.

Immune Checkpoint Molecules on Tumor-Infiltrating Lymphocytes and Their Association with Tertiary Lymphoid Structures in Human Breast Cancer.

There is an exponentially growing interest in targeting immune checkpoint molecules in breast cancer (BC), particularly in the triple-negative subtype where unmet treatment needs remain. This study was designed to analyze the expression, localization, and prognostic role of PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM3 in primary BC. Gene expression analysis using the METABRIC microarray dataset found that all six immune checkpoint molecules are highly expressed in basal-like and HER2-enriched compared to the other BC molecular subtypes. Flow cytometric analysis of fresh tissue homogenates from untreated primary tumors show that PD-1 is principally expressed on CD4+ or CD8+ T cells and CTLA-4 is expressed on CD4+ T cells. The global proportion of PD-L1+, PD-L2+, LAG3+, and TIM3+ tumor-infiltrating lymphocytes (TIL) was low and detectable in only a small number of tumors. Immunohistochemically staining fixed tissues from the same tumors was employed to score TIL and tertiary lymphoid structures (TLS). PD-L1+, PD-L2+, LAG3+, and TIM3+ cells were detected in some TLS in a pattern that resembles secondary lymphoid organs. This observation suggests that TLS are important sites of immune activation and regulation, particularly in tumors with extensive baseline immune infiltration. Significantly improved overall survival was correlated with PD-1 expression in the HER2-enriched and PD-L1 or CTLA-4 expression in basal-like BC. PD-1 and CTLA-4 proteins were most frequently detected on TIL, which supports the correlations observed between their gene expression and improved long-term outcome in basal-like and HER2-enriched BC. PD-L1 expression by tumor or immune cells is uncommon in BC. Overall, the data presented here distinguish PD-1 as a marker of T cell activity in both the T and B cell areas of BC associated TLS. We found that immune checkpoint molecule expression parallels the extent of TIL and TLS, although there is a noteworthy amount of heterogeneity between tumors even within the same molecular subtype. These data indicate that assessing the levels of immune checkpoint molecule expression in an individual patient has important implications for the success of therapeutically targeting them in BC.

Expectation and quality of life after aortic valve replacement over 85 years of age match those of the contemporary general population.

BACKGROUND: In the transcatheter aortic valve implantation (TAVI) years, very elderly patients with aortic stenosis (AS) are referred to surgery with reluctance despite excellent hospital outcomes. A poorly assessed outcome of discharged survivors might further overlook the actual efficacy of the surgical strategy in this cohort. We thus evaluated life-expectancy and functional results in discharged survivors over 85 years operated on for AS. METHODS: Between January 2001 and December 2013, 57 consecutive patients aged ≥85 years underwent aortic valve replacement (AVR) with or without concomitant procedures at our institution. Late survival rate (SR), New York Heart Associaion (NYHA) functional class and quality of life (RAND SF-36) were assessed. SR and quality of life (QoL) were than compared to the contemporary general population matched for age and gender, as calculated by the Italian National Institute of Statistics. RESULTS: Overall in-hospital mortality was 8.8% (5 pts). In patients without concomitant coronary artery bypass grafting (CABG), in-hospital mortality was 2.9%. Survival at 5 and 9 years was 57.7 ± 8.4% and 17.9 ± 11.4%, respectively. No predictors of late mortality including concomitant CABG were identified at Cox analysis. The mean NYHA class for long-term survivors improved from 3.1 to 1.6 (p<0.001). Survivors reported better QoL-scores compared to the age- and gender-matched contemporary general population in 4 RAND SF-36 domains. Life-expectancy resulted comparable to that predicted for the age and gender-matched general population. CONCLUSIONS: Isolated AVR in patients aged ≥85 years can be performed with acceptable risk. Survivors improve in NYHA class and, when compared to age- and gender-matched individuals, show a similar life expectancy and a no lower QoL.

Reduction of group A beta-hemolytic streptococcus pharyngo-tonsillar infections associated with use of the oral probiotic Streptococcus salivarius K12: a retrospective observational study.

Recurrent pharyngo-tonsillar infections caused by group A beta-hemolytic streptococci (GABHS) occur frequently in young children, and the treatment of these infections contributes substantially to the total current requirement for antibiotic prescribing. Our study goal was to assess through a retrospective observational analysis whether the administration of the oral probiotic, Streptococcus salivarius K12 (SsK12), could reduce the occurrence of GABHS pharyngo-tonsillar infections in children who had a recent history of recurrent episodes of these infections. Twelve primary care pediatricians identified, through their databases, a total of 130 children who had experienced recurrent GABHS pharyngo-tonsillar infections over a period of at least 6-12 months prior to their inclusion in the study. Of these children, 76 then undertook a 90-day program requiring once-a-day dosing with a commercially available (Bactoblis) lozenge containing SsK12. No probiotic supplement was given to the remaining 54 (control) children. Each subject was monitored for the occurrence of GABHS pharyngo-tonsillitis and also for acute otitis media, bronchitis, sinusitis, and bronchopneumonia for at least 12 months following their entry to the study. Even 9 months after the use of SsK12 had been stopped, the probability of new GABHS infections was significantly lower (P>0.001) when compared to the period before dosing commenced. When compared to the untreated children, those taking SsK12 appear to have had significantly fewer GABHS infections both during the 90-day period of prophylaxis and during the following 9 months (P<0.001). These observations are supportive of the use of probiotic SsK12 for the control of recurrent GABHS pharyngo-tonsillar infections in children, and as an associated benefit, the use of this probiotic could lead to reduced antibiotic consumption. Follow-up controlled prospective studies should now be initiated in order to further establish the efficacy of this newly emerging prophylactic strategy.

Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study.

Dental caries is the most common chronic disease of childhood. Cariogram is a well-recognized algorithm-based software program based on different caries-related risk factors and intended to aid clinicians in performing more objective and consistent dental caries risk assessments. This type of approach precedes the diagnosis of caries and allows the dentist to identify at-risk patients and then take appropriate preventive measures before caries develop further. One of the etiological factors favoring the development of dental caries is the mutans streptococci. These acidogenic dental plaque inhabitants can be effectively antagonized by the activity of bacteriocins released by the probiotic Streptococcus salivarius M18 (salivarius M18). Moreover, salivarius M18 after colonizing the human oral mucosa produces the enzymes dextranase and urease that are able to counteract plaque formation and saliva acidity, respectively. Seventy-six subjects at high risk of dental caries were randomized and then either treated or not treated for 90 days with an oral formulation containing the oral probiotic salivarius M18 (Carioblis(®)). The results indicate that the use of salivarius M18 increases the chances of avoiding new dental caries development in children, and its application could be proposed as a new tool in the dentist's armory to be adopted in subjects considered at high risk on the basis of their Cariogram outcome.

Use of Streptococcus salivarius K12 in the prevention of streptococcal and viral pharyngotonsillitis in children.

BACKGROUND: Streptococcus salivarius K12 is an oral probiotic strain releasing two lantibiotics (salivaricin A2 and salivaricin B) that antagonize the growth of S. pyogenes, the most important bacterial cause of pharyngeal infections in humans also affected by episodes of acute otitis media. S. salivarius K12 successfully colonizes the oral cavity, and is endowed with an excellent safety profile. We tested its preventive role in reducing the incidence of both streptococcal and viral pharyngitis and/or tonsillitis in children. MATERIALS AND METHODS: We enrolled 61 children with a diagnosis of recurrent oral streptococcal disorders. Thirty-one of them were enrolled to be treated daily for 90 days with a slow-release tablet for oral use, containing no less than 1 billion colony-forming units/tablet of S. salivarius K12 (Bactoblis®), and the remaining 30 served as the untreated control group. During treatment, they were all examined for streptococcal infection. Twenty children (ten per group) were also assessed in terms of viral infection. Secondary end points in both groups were the number of days under antibiotic and antipyretic therapy and the number of days off school (children) and off work (parents). RESULTS: The 30 children who completed the 90-day trial with Bactoblis® showed a significant reduction in their episodes of streptococcal pharyngeal infection (>90%), as calculated by comparing the infection rates of the previous year. No difference was observed in the control group. The treated group showed a significant decrease in the incidence (80%) of oral viral infections. Again, there was no difference in the control group. With regard to secondary end points, the number of days under antibiotic treatment of the treated and control groups were 30 and 900 respectively, days under antipyretic treatment 16 and 228, days of absence from school 16 and 228, and days of absence from work 16 and 228. The product was well tolerated by the subjects, with no side effects, and only one individual reported bad product palatability and dropped out. CONCLUSION: Prophylactic administration of S. salivarius K12 to children with a history of recurrent oral streptococcal disease resulted in a considerable reduction of episodes of both streptococcal and viral infections and reduced the number of days under antibiotic and/or antipyretic therapy and days of absence from school or work.