Rotavirus immunisation status affects the efficacy of Lacticaseibacillus rhamnosus GG for the treatment of children with acute diarrhoea: a meta-analysis.

The efficacy of Lacticaseibacillus rhamonosus GG (LGG) for the treatment of children with acute gastroenteritis has been debated based on most recent evidence. Previous evidence demonstrated that LGG mainly benefits children with Rotavirus infection compared to other aetiologies. However, Rotavirus immunisation (RVI) has been implemented worldwide since 2006. We aimed to investigate whether the efficacy of LGG in children with gastroenteritis vary according to RVI status. The MEDLINE, Embase and Cochrane library databases were searched for relevant randomised controlled trials (RCT) up to April 2022. The duration of diarrhoea and episodes lasting >48 h were considered as primary outcomes. The date of vaccine introduction and RVI coverage were reviewed for all countries where trials were conducted. Among the 15 RCTs included in the analysis (n=3,465), only 5 showed a low risk of bias. In RCT conducted before the introduction of RVI (n=2,932), LGG was effective in reducing the duration of diarrhoea compared with placebo or standard care (Median -23.80 h, 95% confidence interval (CI) -36.59 to -11.02]). Only 2 RCTs (n=1,072) reported data of populations partially immunised against Rotavirus with an overall coverage of 44 and 67%, respectively. In this population, LGG showed no efficacy in reducing the duration of diarrhoea (Median -5.34, 95%CI -12.9 to 2.22). Similarly, LGG reduced the risk of diarrhoea lasting >48 h in children not immunised against Rotavirus (RR 0.73, 95%CI 0.54-0.99), but not in population partially immunised (RR 0.98, 95%CI 0.87 to 1.11). The implementation of RVI might affect the efficacy of LGG modifying local epidemiology and susceptibility of the target population to selected probiotics.

Reduction in broad-spectrum antimicrobial prescriptions by primary care pediatricians following a multifaceted antimicrobial stewardship program.

Background: Since 2016, following the Italian "National Plan to Contrast Antimicrobial Resistance", Campania Region has implemented an antimicrobial stewardship program, including the obligation to associate an appropriate International Classification of Diseases-9 code to each antibiotic prescription, the publication of schemes for empirical antibiotic therapy and educational interventions. Methods: To evaluate the impact of these interventions on the prescribing habits of family pediatricians, we conducted a retrospective cohort study (January 2016-December 2020), including all patients registered in an associate practice of Primary Care Pediatricians. We collected data on antibiotic prescriptions through a specific study management software; our primary outcomes were the annual prescription rates, calculated for both the number of patients in follow-up and the number of medical consultations, and the annual prescription rates for selected antibiotic classes and molecules. To investigate the hypothesis that chronic conditions would be associated with an increased rate of prescription, we also tested the association between underlying conditions and the number of antibiotics received. Results: During the study period, 2,599 children received 11,364 antibiotic prescriptions (mean 4.37, SD 4.28). From 2016 to 2020 we observed a substantial reduction in both the annual prescription rate per 100 patients (9.33 to 3.39; R 2 = 0.927, p = 0.009), and the annual prescription rate per 100 medical consultations (25.49 to 15.98; R 2 = 0.996, p < 0.01). The prescription rates of Amoxicillin-Clavulanate (50.25 to 14.21; R 2 = 0.983, p = 0.001) and third generation Cephalosporins (28.43 to 5.43; R 2 = 0.995, p < 0.01) significantly decreased; we didn't find significant modifications in the prescription rates of Amoxicillin and Quinolones; finally, we observed a trend toward reduction in the prescription of Macrolides. No statistical association was found between antibiotics prescribing frequency and history of chronic diseases. Discussion: Following the implementation of the regional interventions on antimicrobial stewardship, we observed a substantial reduction in the overall antibiotic prescription per patients and per medical consultations, with a statistically significant reduction in the use of broad-spectrum molecules. Considering the results of our analysis, new guidance and training interventions addressed to specialists in the primary care sector should be implemented to further limit antibiotic resistance.

Clostridium difficile infection in children: epidemiology and risk of recurrence in a low-prevalence country.

Clostridium difficile infection (CDI) is increasingly found in children worldwide, but limited data are available from children living in southern Europe. A 6-year retrospective study was performed to investigate the epidemiology, clinical features, treatment, and risk of recurrence in Italy. Data of children with community- and hospital-acquired CDI (CA-CDI and HA-CDI, respectively) seen at seven pediatric referral centers in Italy were recorded retrospectively. Annual infection rates/10,000 hospital admissions were calculated. Logistic regression was used to investigate risk factors for recurrence. A total of 177 CDI episodes was reported in 148 children (83 males, median age 55.3 months), with a cumulative infection rate of 2.25/10,000 admissions, with no significant variability over time. The majority of children (60.8 %) had CA-CDI. Children with HA-CDI (39.2 %) had a longer duration of symptoms and hospitalization (p = 0.003) and a more common previous use of antibiotics (p = 0.0001). Metronidazole was used in 70.7 % of cases (87/123) and vancomycin in 29.3 % (36/123), with similar success rates. Recurrence occurred in 16 children (10.8 %), and 3 (2 %) of them presented a further treatment failure. The use of metronidazole was associated with a 5-fold increase in the risk of recurrence [odds ratio (OR) 5.18, 95 % confidence interval (CI) 1.1-23.8, p = 0.03]. Short bowel syndrome was the only underlying condition associated with treatment failure (OR 5.29, 95 % CI 1.17-23.8, p = 0.03). The incidence of pediatric CDI in Italy is low and substantially stable. In this setting, there is a limited risk of recurrence, which mainly concerns children treated with oral metronidazole and those with short bowel syndrome.

Recommendations for the diagnosis of pediatric tuberculosis.

Tuberculosis (TB) is still the world's second most frequent cause of death due to infectious diseases after HIV infection, and this has aroused greater interest in identifying and managing exposed subjects, whether they are simply infected or have developed one of the clinical variants of the disease. Unfortunately, not even the latest laboratory techniques are always successful in identifying affected children because they are more likely to have negative cultures and tuberculin skin test results, equivocal chest X-ray findings, and atypical clinical manifestations than adults. Furthermore, they are at greater risk of progressing from infection to active disease, particularly if they are very young. Consequently, pediatricians have to use different diagnostic strategies that specifically address the needs of children. This document describes the recommendations of a group of scientific societies concerning the signs and symptoms suggesting pediatric TB, and the diagnostic approach towards children with suspected disease.

The functional effects of nutrients on enterocyte proliferation and intestinal ion transport in early infancy.

Nutrition has a key role in the modulation of the developing intestine in early infancy, and nutrients are able to modulate several intestinal functions including nutrient absorption, ion transport, cell growth and differentiation, motility and immunomodulation. Such modulation is exerted in part through a direct interaction between a single nutrient and the enterocyte. Two functions--ion transport and cell growth--are closely connected and appear to be modulated by nutrients. This is supported by the finding that a single nutrient (e.g. zinc) stimulates ion absorption and also promotes enterocyte growth. Interestingly, intracellular signalling for either effect is similar and involves mitogen-activated protein kinase. Other nutrients also modulate enterocyte function and there is evidence that their effect may depend on their side of action (apical or basolateral) and concentration. Knowledge of the interaction between nutrients and enterocytes may be exploited to obtain clinical effects using nutrition as a long-term treatment for intestinal and non-intestinal conditions.

The non-specific hypersensitivity of the upper and lower airways in Reinke's edema: preliminary results.

Reinke's edema is characterized by swelling of the vocal cords, which generally is bilateral but often is more pronounced in one cord. The disease is named after the anatomist Reinke, who undertook a morphological study of the subepithelial connective tissue of the vocal cords in order to investigate edematous spread. In general, swelling of the vocal cords develops gradually and may increase considerably over months or even years. To evaluate an eventual relation ship between airways (nasal and bronchial) and Reinke's edema of the vocal cords, the authors studied 9 subjects suffering from Reinke's edema. These patients underwent to an accurate clinical history, skin-test for inhalant pollens and mycetes to evaluate the eventual presence of specific allergies, non-specific nasal provocation test with Histamine, baseline RRM to evaluate the non-specific nasal hypersensitivity and besides the RRM values has been considered the number of sneezes after Histamine stimulation, finally a bronchial provocation test with ultrasonic fog to evaluate the presence of non-specific hypersensitivity of the lower airways.

Research of non-specific hyperreactivity of upper airways in subjects with gastro-esophageal reflux (G.E.R.): preliminary reports.

An association between asthma and gastro-esophageal reflux (GER) is well recognized but the underlying mechanism is still unclear. The authors suggest that could exist an association between GER and upper airways hyperreactivity and this association could represents the mechanism underlying the lower esophageal sphincter releasing, that determine the reflux. In fact they suppose that, the noxious injury of acid reflux follows a course that could be: pharynx-->larynx-->bronchi-->1/3 inferior of the esophagus-->reflux. From these presuppositions the authors carried out a study on the possible relationship between GER and non-specific hyperreactivity of upper airways on 14 subjects, divided in 2 groups: 10 subjects with functional GER, 4 subjects suffering from GER caused by hiatus hernia as control group. All patients had a thorough medical history, ENT examination with rigid and flexible endoscope, anterior Rhinomanometry (RRM), skin-test for inhalant and alimentary allergens, RAST, audiometric exam, non-specific nasal provocation test (NSNPT) with histamine, using as control the number of sneezes. From a through analysis of objective examination and from the results of the NSNPT with histamine resulted that all subjects with functional GER were rhinopathics. In all tests both in vivo (Skin-test) and in vitro(RAST) for the most common allergens (pollens-inhalant-mycophites-alimentary) the results were negative. The authors also found an involvement of paranasal sinuses that raised: 91% in the patients with recurrents phlogosis due to non specific nasal hyperreactivity; 40.9% in the allergic subjects (20% in the Graminacee +; 32% in the Parietaria O. +; 76% in the Dermatophagoides Pt. +; others 4%); 100% in the ASA-intolerance subjects. The NSNSPT with histamine showed in the group with functional GER a hyperreactivity with sneezes in 6/10 subjects, and 1/4 subjects of the group with GER with hiatus hernia. The RRM variations showed an unilateral nasal hyperreactivity in 6/10, bilateral in 3/10 subjects of the group with functional GER. In the group with GER with hiatus hernia only 1/4 subject showed reliable unilateral RRM variation. From the analysis of data resulted that subjects with functional GER showed a completely involvement of the upper airways and not only of the pharynx and larynx, caused by non specific hyperreactivity at the NSNPT with histamine, associated with a chronic pathology.

The behaviour of non-specific nasal provocation tests in subjects with allergic rhinitis and not, in and out of crisis. A longitudinal study.

The non specific nasal hypersensitivity (N.S.N.H.) is characterized by an exaggerated reaction towards various non-specific stimuli in rhinopathic subjects. This N.S.N.H. involves the afferent structure of nasal mucosa, the effector organ and the central modulation system. The physiopathogenetic and clinical implications induced the authors to study the N.S.N.H. behaviour in 218 subjects divided into 5 groups, as follows: control group, subjects with perennial rhinitis of non allergic origin, subjects with seasonal rhinitis due to allergy towards Graminaceae during seasonal crisis and not, subjects with perennial rhinitis due to allergy towards Dermatophagoides pteronissinus. All subjects moreover have been subdivided according to the years of illness. The N.S.N.H. behaviour has been studied with non-specific nasal provocation tests with methacholine, cold water solution and histamine, so the amount of sneezes were assessed. The results show a reduction of the reaction, previously high, to methacholine and cold water solution tests after 6-12 years of illness in subjects with perennial rhinitis, while the test with histamine always gives higher results. This could mean a reduction of N.S.N.H. during the years of illness, probably connected to the answer of the effector organ, without involvement of that afferent portion of nasal mucosa.

Rhinoreactivity in a patient affected by the Darier-White disease.

The Darier-White disease is a rare hyperkeratosic skin-disease which can also affect other organs. From an otoiatric point or view, there are alterations of the oral cavity, salivary glands and congenital deafness, but there is nothing against the nasal mucosa. The clinical case we studied, shows the presence of aspecific nasal hyperreactivity correlated to sun exposure as it happens for cutaneous lesions, independently of the presence of eosinophiles in the nasal secretion. This could mean that the Darler-White disease can also alter the function of the nasal mucosa.