Effectiveness of bismuth subgallate for preventing bleeding following adenotonsillectomy: A multicentre study.

BACKGROUND: Tonsillectomy and adenotonsillectomy are surgical procedures routinely performed worldwide, with various complications, including postoperative bleeding (PTH). Among haemostatic agents, bismuth subgallate (BS) has been employed in the past decades, but its use is controversial in children. OBJECTIVE: This retrospective, multicentre study aims to evaluate the effectiveness and safety of BS in preventing PTH following tonsillectomy and adenotonsillectomy. MATERIALS AND METHODS: Two cohorts of children between 0 and 18 years of age were compared in two different hospitals. The first (active) group of patients included children who underwent tonsillectomy/adenotonsillectomy performed using BS added to gauze swabs, whereas this agent was not administered to the second (control) group. The following variables were analysed: age, gender, degree of tonsillar hyperplasia, length of hospital stay, acute complications (including bleeding and infection), further admissions to the Paediatric Emergency Department (PED), and further hospital admissions in the 30 days postoperatively. RESULTS: Four-thousand- seven hundred forty-four children were included in the study, 2598 in the active group and 2146 in the control group. The cases included in the active treatment group displayed a significantly reduced PTH prevalence, 1.4 versus 2.6 % (p < 0.05). No cases of neurological complications or aspiration pneumonia were detected. CONCLUSIONS: This study supports BS as a safe and reliable option for preventing severe PTH following tonsillectomy/adenotonsillectomy.

Proteomic Study Identifies Glycolytic and Inflammation Pathways Involved in Recurrent Otitis Media.

Recurrent acute otitis media (RAOM) in children is clinically defined as the occurrence of at least three episodes of acute otitis media over a course of 6 months. A further common pathological condition of interest in the context of pediatric otolaryngology is adenotonsillar hypertrophy (ATH), a common cause of obstructive sleep apnea syndrome. Aimed at unraveling the differential modulation of proteins in the two pathologies and at understanding the possible pathways involved in their onset, we analyzed the proteomic profile of the adenoids from 14 RAOM and ATH patients by using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). The 2-DE coupled with MS allowed us to identify 23 spots with significant (p-value < 0.05) changes in protein amount, recognizing proteins involved in neutrophil degranulation and glycolysis pathways.

Combined intranasal fentanyl and dexmedetomidine plus inhaled nitrous oxide sedation in children needing myringotomy and ventilation tube insertion with a specific handheld device.

OBJECTIVES: We report a case series of one-time 4 mcg/kg dose of intranasal dexmedetomidine and 1 mcg/kg of intranasal fentanyl plus inhaled nitrous oxide for procedural sedation in children with otitis media with effusion (OME) for tympanostomy tube placement with a specific handheld device (Solo TTD, AventaMed ®). METHODS: A retrospective review was conducted in a tertiary paediatric teaching hospital on patients with OME referred from December 2018 to December 2019 in need of procedural sedation for myringotomy and ventilation tube insertion (VTI). Sixteen of twenty-four consecutively admitted subjects received a one-time dose (4 mcg/kg) of intranasal dexmedetomidine and 1mcg/Kg of intranasal fentanyl followed by inhaled nitrous oxide (iN2O) at 50% with the intended goal to achieve a Ramsay Sedation Score 4 allowing a motionless procedure with adequate analgesia. Parents' satisfaction for the procedure was measured by mean of a Likert scale (from 0 to 5 points). RESULTS: Sixteen patients underwent procedural sedation for myringotomy with VTI. Sedation was achieved successfully in fifteen patients (93,75%), with a mean induction time of 29 min (range 19-43) and a mean recovery time of 74 min (range 54-110). The patient who did reach an adequate sedation level underwent an intravenous line positioning and a dose of ketamine. No adverse effects were reported, and the parents' judgment average on the Likert scale was 4,93. VTI procedure was successful in all ears. CONCLUSIONS: A combination of intranasal dexmedetomidine, fentanyl, and iN2O could be considered as a possible option for procedural sedation in children with OME undergoing procedural sedation for tympanostomy tube placement in children with Solo TTD device.

Copy number variation, gene expression and histological localization of human beta-defensin 2 in patients with adeno-tonsillar hypertrophy.

Both bacterial infections and innate oral immunity response participate in development of adeno-tonsillar hypertrophy (ATH). ATH can lead to obstructive sleep apnea. We investigated the beta-defensin 2 (hBD-2) encoding gene, DEFB4, by analyzing the copy number variations (CNVs) of the defensin gene cluster in patients with ATH and by correlating CNV with DEFB4 gene expression. We enrolled 79 patients with ATH, 21 of whom presented with only adenoid hypertrophy, while 58 exhibited hypertrophy of both adenoid and tonsil. CNVs of the defensin gene cluster, DEFB4 mRNA, and hBD-2 protein expression were assessed. Also, beta-defensin 2 was localized histologically using immunohistochemistry. The distribution of defensin gene cluster CNV was similar among the 79 subjects. DEFB4 expression analysis exhibited considerable inter-individual variability, but with neither specific differences among subjects nor correlation with the CNV number. Immunohistochemistry enabled localization of hBD-2 in the tonsil and adenoid epithelium. No differences in localization between the two ATH presentations were found. Inducible antimicrobial defensin peptides exhibited great inter-individual variability in terms of both CNV and gene expression, but no correlation with presentation of ATH was found.

Detection of epidermal thickening in GJB2 carriers with epidermal US.

PURPOSE: To measure epidermal thickness by using skin ultrasonography (US) in a series of healthy control subjects and obligate carriers for the worldwide most frequent form of congenital hearing loss owing to the mutated alleles of the connexin 26 gene (GJB2). MATERIALS AND METHODS: The patent for the protocol, coupled with a new sonographic probe specifically designed to analyze epidermal thickness and a dedicated algorithm to classify individuals in groups, is pending. Institutional ethics committee approval and patient consent were obtained. After a preliminary study in 23 subjects aimed to define the best body site and instrument and protocol for US, a total of 303 individuals (237 healthy subjects, 51 carriers, and 15 homozygotes) were tested at midline forehead by using a linear large-band probe with a frequency ranging from 6 to 15 MHz to determine epidermal thickness. Variance and linear regression analyses were performed. Regression coefficients were then used to obtain measurements of thickness corrected for age and sex. RESULTS: GJB2 obligate carriers had a significant increase in epidermal thickness compared with control subjects. GJB2 status explains about 50.0% of this variability, whereas an additional 25.0% is explained by sex and age. Results led to the development of a possible screening protocol with a 98.0% sensitivity and 92.8% specificity in subjects aged 2080 years, with a likelihood ratio of a positive test of 14:1. Even better results (100% sensitivity and 98.9% specificity) were obtained in an analysis of people of only reproductive age. CONCLUSION: Epidermal thickening in the white population owing to GJB2 carrier status can be detected by using US. This measurement could provide a simple, noninvasive, rapid, and sensitive test for carrier screening.

Age-related hearing loss in four Italian genetic isolates: an epidemiological study.

The objective of this study was to estimate the prevalence of hearing impairment in four genetically isolated Italian villages (Carlantino, Campora, Gioi-Cardile, and Stoccareddo), 1682 subjects were recruited from all the individuals participating in a multidisciplinary study. They underwent otoscopy and pure-tone audiometry and completed a questionnaire. The audiological data show that the percentage of impaired people increases with age and in particular becomes relevant aged over 40. For this reason we decided to compare the PTA values of individuals aged 40 or older. The PTA values of Stoccareddo and Carlantino are statistically different from PTAs of the other villages. Campora and Gioi-Cardile, both located within the Cilento National Park, have similar middle-low frequency PTA values while some differences are present at high frequencies. Using pedigrees it was possible to calculate the heritability of the trait. For Carlantino and Gioi-Cardile the percentage of the phenotype variation attributable to genetic variation is not significant, while for Campora the heritability value is 0.49 (p = 0.01) suggesting that genetic factors may have an important role.

Human beta defensin-1 is involved in the susceptibility to adeno-tonsillar hypertrophy.

INTRODUCTION: Innate immunity molecules are known to play a pivotal role in the homeostasis of the oral mucosa, permitting the presence of commensal microflora and, at the same time, providing a first line of defense against pathogens attempting to invade the oral cavity. Tonsils represent the local immune tissue in oral cavity, being able to provide a non-specific response to pathogens; however, in the presence of microbes or foreign materials present in the mouth tonsils could became infected and develop chronic inflammation, thus leading to hypertrophy. The etiology of the disease is multifactorial depending upon environmental and host factors, the latter including molecules of mucosal innate immunity. METHODS: Ninety-five children with adeno-tonsillar hypertrophy subjected to adeno-tonsillectomy were recruited at the pediatric otorhinolaryngology service of the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste (Italy). The specimen discarded from the surgery were used for genomic DNA extraction and genotyping, for mRNA extraction and gene expression analysis, finally the samples were cut and used to prepare slides to perform immunohistochemistry. RESULTS: Functional polymorphisms within DEFB1 gene, encoding the human beta defensin-1 (hBD-1), were analyzed finding association between DEFB1 rare haplotypes and susceptibility to adeno-tonsillar hypertrophy. DEFB1 mRNA expression was detected in the tonsils and the hBD-1 protein was localized at the epithelia of tonsils mainly in the proximity of the basal lamina. CONCLUSION: Our findings lead us to hypothesize an involvement of hBD-1 mediated innate immunity in the modulation of the susceptibility towards adeno-tonsillar hypertrophy development.

Neither hereditary periodic fever nor periodic fever, aphthae, pharingitis, adenitis: Undifferentiated periodic fever in a tertiary pediatric center.

AIM: To describe the frequency and clinical characteristics of patients with undifferentiated periodic fever (UPF) and to investigate whether a clinical classification of UPF based on the PRINTO-Eurofever score can help predicting the response to treatment and the outcome at follow-up. METHODS: Clinical and therapeutic information of patients with recurrent fever who presented at a single pediatric rheumatology center from January 2006 through April 2016 were retrospectively collected. Patients with a clinical suspicion of hereditary periodic fever (HPF) syndrome and patients with clinical picture of periodic fever, aphthae, pharingitis, adenitis (PFAPA) who were refractory to tonsillectomy underwent molecular analysis of five HPF-related genes: MEFV (NM_000243.2), MVK (NM_000431.3), TNFRSF1A (NM_001065.3), NLRP3 (NM_001079821.2), NLRP12 (NM_001277126.1). All patients who had a negative genetic result were defined as UPF and further investigated. PRINTO-Eurofever score for clinical diagnosis of HPF was calculated in all cases. RESULTS: Of the 221 patients evaluated for periodic fever, twelve subjects with a clinical picture of PFAPA who were refractory to tonsillectomy and 22 subjects with a clinical suspicion of HPF underwent genetic analysis. Twenty-three patients (10.4%) resulted negative and were classified as UPF. The median age at presentation of patients with UPF was 9.5 mo (IQR 4-24). Patients with UPF had a higher frequency of aphthae (52.2% vs 0%, P = 0.0026) and musculoskeletal pain (65.2% vs 18.2%, P = 0.0255) than patients with genetic confirmed HPF. Also, patients with UPF had a higher frequency of aphthous stomatitis (52.2% vs 10.7%, P < 0.0001), musculoskeletal pain (65.2% vs 8,0%, P < 0.0001), and abdominal pain (52.2% vs 4.8%, P < 0.0001) and a lower frequency of pharyngitis (56.6% vs 81.3%, P = 0.0127) compared with typical PFAPA in the same cohort. Twenty-one of 23 patients with UPF (91.3%) received steroids, being effective in 16; 13 (56.2%) were given colchicine, which was effective in 6. Symptoms resolution occurred in 2 patients with UPF at last follow-up. Classification according to the PRINTO-Eurofever score did not correlate with treatment response and prognosis. CONCLUSION: UPF is not a rare diagnosis among patients with periodic fever. Clinical presentation place UPF half way on a clinical spectrum between PFAPA and HPF. The PRINTO-Eurofever score is not useful to predict clinical outcome and treatment response in these patients.

MBL2 genetic polymorphisms in Italian children with adenotonsillar hypertrophy.

We investigated the role of the polymorphisms in the first exon of MBL2 gene in the susceptibility to recurrent tonsillitis in a selected group of Italian children and healthy controls. Significant difference has been observed in MBL2 genotype and allelic frequencies between children with recurrent tonsillitis and healthy controls matched for sex and age. Children characterized by a "low MBL" producer genotype, namely 00, are more prone to recurrent tonsillitis when compared to the healthy controls. To our knowledge this is the first report on the role of MBL2 polymorphisms in adenotonsillar hypertrophy and our results shown that presence of MBL2 00 genotype could be used as a prognostic marker in subjects with adenotonsillar hypertrophy.

Non tuberculous mycobacteria infection of the parotid region: two familiar cases.

OBJECTIVE: We review two cases of non tuberculous mycobacteria infections of the parotid region in members of the same family. The parotid region represents a peculiar location for the disease and it is exceptional to discover cases in members of the same family. METHODS: Two unusual case reports of non tuberculous mycobacteria infections in two members of the same family are presented. We discuss the diagnostic criteria and review pertinent recent literature. To our knowledge, these are the first English language reports of NTM infections in member of the same family. RESULTS: We performed surgical exeresis of the lesions in parotid region together with the skin affected by the fistula; regular check-ups for 24 months after surgery. CONCLUSIONS: Surgical exeresis of regional structures is the treatment for non tuberculous mycobacteria infections non responsive to antibiotic therapy.

Lactoferrin gene polymorphisms in Italian patients with recurrent tonsillitis.

INTRODUCTION: Recurrent tonsillitis is an oral pathology characterized by inflammation of tonsils. The disease susceptibility depends upon environmental and host factors, specifically the innate immune response, the first line of host defence could play an important role. Among innate immunity members, lactoferrin, known for its antimicrobial properties, was previously correlated with the risk of oral pathology as periodontitis and dental caries. METHODS: 89 Italian children presenting recurrent tonsillitis and 95 healthy children were genotyped for two LTF non-synonymous polymorphisms, called Thr29Ala and Arg47Lys, in order to investigate their potential role in recurrent tonsillitis susceptibility. RESULTS: no different allele, genotype and haplotype frequency distributions were detected comparing patients and controls. CONCLUSION: data from the current study indicate that LTF polymorphisms might not be involved in recurrent tonsillitis development in our Italian population. However, since the importance of lactoferrin in oral immunity has been previously assessed, further studies should be necessary to unravel the potential role of LTF genetic variants in oral cavity.

DEFB1 polymorphisms and susceptibility to recurrent tonsillitis in Italian children.

INTRODUCTION: The tonsils are secondary lymphoid organs fundamental for immune system response against pathogens within the oral cavity. Tonsillitis refers to inflammation of the pharyngeal tonsils that may include the adenoids and the lingual tonsils and that can be acute, recurrent, and chronic. Viral or bacterial infections, as well as immunologic factors are the main trigger to tonsillitis and disease's chronicity: the host immune responses, especially the innate one, could play an important role in susceptibility to the disease. OBJECTIVES: The current study aims at investigating the role of functional polymorphisms in the 5'UTR (c.-52G>A, c.-44G>C and c.-20G>A) of DEFB1 gene, encoding for the antimicrobial peptide human beta-defensin 1, in the predisposition to recurrent tonsillitis in children from North Eastern Italy. RESULTS: No significant correlation was found between DEFB1 allele, genotype and haplotype frequencies and recurrent tonsillitis susceptibility with the exception of an increased risk to disease development in patients carrying DEFB1 rare haplotypes. CONCLUSION: Our results may suggest that DEFB1 polymorphisms alone may not influence pathology susceptibility, however they could possibly concur, together with other factors involved in the genetic control of innate immune system, in the predisposition towards recurrent tonsillitis.

Ear nose throat manifestations in hypoidrotic ectodermal dysplasia.

The ectodermal dysplasias (EDs) are a large and complex group of inherited disorders. In various combinations, they all share anomalies in ectodermal derived structures: hair, teeth, nails and sweat gland function. Clinical overlap is present among EDs. Few causative genes have been identified, to date. Altered gene expression is not limited to the ectoderm but a concomitant effect on developing mesenchymal structures, with modification of ectodermal-mesenchymal signaling, takes place. The two major categories of ED include the hidrotic and hypohidrotic form, the latter more frequent; they differentiate each other for the presence or absence of sweat glands. We report Ear Nose Throat manifestations of ED, linked to the reduction of mucous glands in the nasal fossae with reduced ciliar function, and decrease salivary glands function. Often patients report an increased rate of infections of the upper respiratory tract and of the ear. Nasal obstruction due to the presence of nasal crusting, hearing loss and throat hoarseness are the most represented symptoms. Environmental measures, including a correct air temperature and humidification, is mandatory above all in subjects affected by hypohidrotic form.

MBL expression in patients with recurrent tonsillitis.

OBJECTIVE: We evaluated mannose binding lectin (MBL) protein production and histological localization, MBL2 gene expression and genotypes distribution in patients characterized by recurrent tonsillitis, with the aim of verifying the innate immune response to the infection and inflammation occurring in the tonsils. METHODS: MBL2 exon 1 and promoter polymorphims were detected by PCR amplification and subsequent direct sequencing of the amplicons. Monoclonal antibodies to MBL were used on frozen sections of tonsils for the immunohistochemical localization of MBL protein. MBL Oligomer ELISA kit was used to quantify the level of MBL in the serum of the 30 patients with recurrent tonsillitis. Quantitative RT PCR for the evaluation of MBL2 expression of MBL high producers (HP), low producers (LP) and deficient producers (DP) was performed using the Hs00175093 gene-expression Assay on Demand. RESULTS: The distribution of the MBL2 combined genotypes was as follows: 21 HP (70%; 15 HYA/HYA, 6 HYA/LXA), 6 LP (20%; 5 HYA/0, 1 LXA/LXA) and 3 DP (10%, all 0/0). MBL levels were directly correlated to the MBL2 combined genotypes: HP patients showed higher mean MBL concentration of 4044 ng/mL, LP patients were characterized by a mean of 905 ng/mL whereas those with DP combined genotype presented extremely low levels of MBL (mean value of 74 ng/mL) (p=0.0005). Immunohistochemistry performed on tonsils sections demonstrated that MBL was widely distributed throughout the surface of the basal lamina of all the 21 HP subjects. MBL was undetectable in situ in both LP and DP patients. MBL2 expression, although at very low levels, was found for the HP group, the LP and the DP group as well. CONCLUSIONS: We confirmed the genotype-phenotype correlation of MBL2 gene exon 1 and promoter polymorphisms with the quantitative production of serum MBL, we reported a very low MBL2 expression at local level in tonsils and we determined the in situ localization of MBL in the basal lamina of the tonsils of patients who underwent to tonsillectomy. Our findings suggest an important role of MBL protein in the innate immune response of the tonsil to pathogens, as in recurrent infection and inflammation.